BACKGROUND: To explore the value of a multiparametric magnetic resonance imaging (MRI)-based deep learning model for the preoperative prediction of Ki67 expression in prostate cancer (PCa). MATERIALS: The data of 229 patients with PCa from two centers were retrospectively analyzed and divided into training, internal validation, and external validation sets. Deep learning features were extracted and selected from each patient's prostate multiparametric MRI (diffusion-weighted imaging, T2-weighted imaging, and contrast-enhanced T1-weighted imaging sequences) data to establish a deep radiomic signature and construct models for the preoperative prediction of Ki67 expression. Independent predictive risk factors were identified and incorporated into a clinical model, and the clinical and deep learning models were combined to obtain a joint model. The predictive performance of multiple deep-learning models was then evaluated. RESULTS: Seven prediction models were constructed: one clinical model, three deep learning models (the DLRS-Resnet, DLRS-Inception, and DLRS-Densenet models), and three joint models (the Nomogram-Resnet, Nomogram-Inception, and Nomogram-Densenet models). The areas under the curve (AUCs) of the clinical model in the testing, internal validation, and external validation sets were 0.794, 0.711, and 0.75, respectively. The AUCs of the deep models and joint models ranged from 0.939 to 0.993. The DeLong test revealed that the predictive performance of the deep learning models and the joint models was superior to that of the clinical model (p < 0.01). The predictive performance of the DLRS-Resnet model was inferior to that of the Nomogram-Resnet model (p < 0.01), whereas the predictive performance of the remaining deep learning models and joint models did not differ significantly. CONCLUSION: The multiple easy-to-use deep learning-based models for predicting Ki67 expression in PCa developed in this study can help physicians obtain more detailed prognostic data before a patient undergoes surgery.

Synovial sarcoma (SS) is one of the commonest non-rhabdomyosarcoma soft tissue sarcoma with limited treatment options in the relapsed and advanced settings. The combination of gemcitabine and docetaxel has demonstrated its role predominantly in leiomyosarcoma and pleomorphic sarcomas but has not been prospectively studied in SS. This trial assesses the efficacy, tolerability and quality of life (QoL) with this regimen in metastatic/unresectable locally advanced relapsed SS.Patients and methods This was a single-arm, two-stage, phase II, investigator-initiated interventional study among patients with metastatic or unresectable locally advanced SS who had progressed after at least one line of chemotherapy. Gemcitabine 900 mg/m2 on days 1 and 8 and docetaxel 75 mg/m2 on day 8 were administered intravenously every 21 days. The primary endpoint was 3-month progression-free rate (PFR); overall survival (OS), progression-free survival (PFS), overall response rate (ORR), safety and quality of life (QoL) constituted the secondary endpoints.Results Twenty-two patients were enrolled between March 2020 and September 2021 and the study had to be closed early due to slow accrual. The study population comprised of 18 (81.8%) patients with metastatic disease and 4 (18.2%) patients with locally advanced, unresectable disease. The most common primary sites of disease were extremity in 15 (68%) and the median number of lines of prior therapies received was 1 (range 1-4). 3-month PFR was 45.4% (95% CI 24.8-66.1) and ORR was 4.5%. Median progression-free survival (PFS) was 3 months (95% CI 2.3-3.6) and median OS was 14 months (95% CI 8.9-19.0). 7 (31.8%) patients experienced grade 3 or worse toxicities, including anemia (18%), neutropenia (9%) and mucositis (9%). QoL analysis demonstrated significant decline in certain functional and symptom scales, while financial and global health scales remained stable.Conclusion This is the first prospective study on the combination of gemcitabine and docetaxel performed specifically in patients with advanced, relapsed SS. Although the accrual of patients could not be completed as planned, the therapy did produce clinically meaningful outcomes and met its primary endpoint of 3-month PFR. This result, along with the manageable toxicity profile and stable global health status on QoL analysis, should encourage further studies.Trial registration This trial was prospectively registered under the Clinical Trials Registry of India on 26/02/2020 (Registration number: CTRI/2020/02/023612).

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common human cancers with poor prognosis in the world. HCC has become the second leading cause of cancer-related death in China. It is urgent to identify novel biomarker and valid target to effectively diagnose, treat or predict the prognosis of HCC. It has been reported that S100A family is closely related to cell proliferation and migration of different cancers. However, the values of S100As in HCC remain to be further analyzed. METHODS: We investigated the transcriptional and translational expression of S100As, as well as the value of this family in HCC patients from the various databases. RESULTS: S100A10 was most relevant to HCC. CONCLUSIONS: The results from HCC patients' tissues and different cells also confirmed the role of S100A10 in HCC. Furthermore, we proved that S100A10 could influenced the cell proliferation of HCC cells via ANXA2/Akt/mTOR pathway. However, it would appear that the relationship between S100A10 and HCC is complex and requires more research.

BACKGROUND: Low levels of cancer awareness may contribute to delays in seeking medical help and subsequent delays in diagnosis. For blood cancer this may be a particularly prominent problem due to the high prevalence of undifferentiated symptoms such as bodily pain, weakness, nausea and weight loss, resulting in low symptom awareness. The delay is exacerbated by the dismissal of similar symptoms which are often interpreted as mild disease, resulting in multiple consultations prior to diagnosis. This study describes the development of a Cancer Awareness Measure for Blood Cancer (Blood CAM) and presents results from a population-representative survey using the measure. METHODS: A rapid systematic review identified constructs relevant to blood cancer. Items were taken from previous awareness measures and other literature and reviewed by expert groups including health care professionals and patients. Cognitive interviews were conducted with ten members of the public to check comprehension and clarity. A total sample of 434 participants completed the survey at Time 1 and n = 302 at Time 2 (two weeks later). RESULTS: Internal reliability was high across the different constructs included in the questionnaire (> 0.70) and test-retest reliability was moderate to good (0.49-0.79). The most commonly recognised blood cancer symptoms were unexplained weight loss (68.9%) and unexplained bleeding (64.9%) and the least commonly recognised symptoms were night sweats (31.3%) breathlessness and rash/itchy skin (both 44%). In terms of symptom experience, fatigue was the most commonly reported symptom (26.7%) followed by night sweats (25.4%). Exploratory factor analysis of barriers to presenting at primary care revealed three distinct categories of barriers; emotional, external/practical and service/healthcare professional related. Service and emotional barriers were most common. CONCLUSIONS: We developed a valid and reliable tool to assess blood cancer awareness and showed variable awareness of blood cancer symptoms which can help target public health campaigns. We also incorporated additional measures (e.g. confidence to re-consult, ability to understand symptoms) that could be used to tailor public messaging for blood cancer and for other harder to suspect and diagnose cancers.

BACKGROUND: Few studies have focused on the impact of single-organ pulmonary metastases on progression-free survival and overall survival in patients with metastatic colorectal cancer. Recognizing differences in prognosis and chemotherapeutic efficacy based on metastasized organs may help in optimizing treatment strategies. The exploratory study was conducted to evaluate the comparative clinical outcomes and prognoses of patients with metastatic colorectal cancer presenting with single-organ pulmonary metastases and treated with folinic acid, 5-fluorouracil, irinotecan, and vascular endothelial growth factor inhibitors as second-line chemotherapy. METHODS: This retrospective study included 289 patients with metastatic colorectal cancer treated with second-line folinic acid, 5-fluorouracil, irinotecan, and vascular endothelial growth factor inhibitors. The response rate, disease control rate, progression-free survival, and overall survival were assessed in the participants. RESULTS: Among the 289 patients enrolled, 26 (9.0%) had single-organ pulmonary metastasis with left-sided primary locations, lower levels of tumor markers at the initiation point of chemotherapy, a significantly higher disease control rate (96.2% vs. 76.7%, P = .02), and a longer progression-free survival (median 29.6 months vs. 6.1 months, P < .001) and overall survival (median 41.1 months vs. 18.7 months, P < .001) than patients with other forms of metastatic colorectal cancer. Multivariate analysis showed that single-organ pulmonary metastasis was an independent predictor of longer progression-free survival (hazard ratio 0.35, P = .00075) and overall survival (hazard ratio 0.2, P = .006). CONCLUSION: Single-organ pulmonary metastasis was a strong predictor of progression-free survival and overall survival in patients with metastatic colorectal cancer treated with folinic acid, 5-fluorouracil, irinotecan, and vascular endothelial growth factor inhibitors as second-line chemotherapy; this provides preliminary evidence for medical guidelines and clinical decision-making on novel therapeutic strategies for these patients.

BACKGROUND: Atezolizumab plus bevacizumab was approved in 2020 as a first-line treatment for advanced hepatocellular carcinoma (HCC). The purpose of this study was to assess the curative effect and tolerability of the combination treatment in advanced HCC. METHODS: Web of Science, PubMed and Embase were retrieved for qualified literatures on the treatment of advanced HCC with atezolizumab plus bevacizumab until September 1, 2022. The outcomes included pooled overall response (OR), complete response (CR), partial response (PR), median overall survival (mOS), median progression-free survival (mPFS), and adverse events (AEs). RESULTS: Twenty-three studies, comprising 3168 patients, were enrolled. The pooled OR, CR, and PR rates of the long-term (more than six weeks) therapy response based on Response Evaluation Criteria in Solid Tumors (RECIST) were 26%, 2%, and 23%, respectively. The pooled OR, CR, and PR rates of the short-term (six weeks) therapeutic response evaluated with RECIST were 13%, 0%, and 15%, respectively. The pooled mOS and mPFS were 14.7 months and 6.66 months, respectively. During the treatment, 83% and 30% of patients experienced any grade AEs and grade 3 and above AEs, respectively. CONCLUSIONS: Atezolizumab in combination with bevacizumab showed good efficacy and tolerability in the treatment of advanced HCC. Compared with short-term, non-first-line, and low-dose therapy, atezolizumab plus bevacizumab in long-term, first-line, and standard-dose treatment for advanced HCC showed a better tumor response rate.

BACKGROUND: Cervical cancer is one of the most common cancers and a major cause of morbidity among women globally. Chemoradiation therapy is the preferred standard treatment for women with stage IB to IVA. However, the benefits of this treatment can only be achieved if patients adhere to the treatment guidelines. In this study, the proportion of compliance or adherence to chemo-radiation treatment among cervical cancer patients at Uganda Cancer Institute (UCI) was determined. METHODS: This was a cross-sectional study that reviewed data retrospectively for 196 cervical cancer patients who were prescribed to chemo-radiation therapy at UCI between November 2020 to May 2021, having been diagnosed with disease stage IB to IVA. Patient data and information on treatment uptake was obtained by review of the patient's medical records. Treatment compliance was determined by calculating the number of participants who completed the prescribed treatment (definitive pelvic concurrent chemoradiation to 50 Gy external beam radiotherapy with weekly concurrent cisplatin followed by intracavitary brachytherapy 24 Gy in 3 fractions at 8 Gy once a week over 3 weeks). Associations between patient factors and treatment adherence were determined using logistic regression analysis. In all statistical tests, a P- value of < 0.05 was considered as significant. RESULTS: The proportion of patients who were administered with external beam radiation (EBRT), chemotherapy and brachytherapy were 82.6%, 52.04% and 66.2% respectively. However, only 23 of 196 patients (11.7%) were found to have adhered to the treatment plan by completion of all definitive pelvic concurrent chemoradiation to 50 Gy external beam radiotherapy (5 weeks) with weekly concurrent cisplatin (5 cycles) followed by intracavitary brachytherapy 24 Gy in 3 fractions at 8 Gy once a week over 3 weeks (3 sessions). There were no significant associations between patient factors and treatment adherence after multivariable analysis. CONCLUSIONS: Treatment compliance was found in only 12% of the cohort participants. No association of patient factors with treatment compliance was found. Additional studies on treatment adherence with larger sample sizes are needed to confirm the associations.

BACKGROUND: To include the patient perspective in the assessment of adverse events in oncology, a patient-reported outcomes (PRO) version of the Common Terminology Criteria for Adverse Events (CTCAE) was developed by the US National Cancer Institute, the so called PRO-CTCAE. The objective of this study was the development of disease-specific PRO-CTCAE item sets for patients with breast cancer (BC), multiple myeloma (MM), and prostate cancer (PC). METHODS: The cross-sectional survey was conducted at three German outpatient cancer centers. Prevalence and importance of the 78 PRO-CTCAE symptoms were assessed using a patient questionnaire. To select the most relevant PRO-CTCAE items for each tumor entity, symptoms were ranked based on patient answers. RESULTS: 101 patients with BC, 107 with MM, and 66 with PC participated. The final item sets contained 21 symptoms (BC) or 19 symptoms (MM and PC), respectively. Eight symptoms (fatigue, muscle pain, insomnia, joint pain, general pain, dizziness, shortness of breath, and swelling) were represented in all three item sets. Fatigue was the symptom with the highest ranking across item sets followed by insomnia. Symptoms with the highest rankings represented in only one item set were symptoms affecting the urogenital system in the PC item set, blurred vision in the BC item set, and decreased appetite in the MM item set. CONCLUSIONS: Individual PRO-CTCAE item sets for a German patient population were developed for the three tumor entities on the basis of patients' differences in symptom profiles and perceptions. The quality and psychometric criteria of the newly compiled item sets should be evaluated in validation studies.

OBJECTIVE: Multiple myeloma is a heterogeneous disorder and the intratumor genetic heterogeneity contributes to emergency of drug resistance. Dexamethasone has been used clinically for decades for MM. Nevertheless, their use is severely hampered by the risk of developing side effects and the occurrence of Dex resistance. LncRNA NEAT1 plays a oncogenic role and participates in drug resistance in many solid tumors. Therefore, we investigated a potential usefulness of this molecular as a biomarker for diagnosis of MM and possible correlations of NEAT1 expression with drug resistance and prognosis. METHODS: Bone marrow and peripheral blood mononuclear cells samples were collected from 60 newly diagnosed MM patients. The expression of NEAT1expression level were detected by quantitative real-time PCR analyses. The relationship about the expression levels of lncRNA with other clinical and cytogenetic features was analyzed. In addition, we measured to analysis the correlation between the expression of NEAT1 and Dex resistance in MM patients. RESULTS: It was found that the expression of NEAT1 is significantly higher in multiple myeloma patients compared to controls and does not change with other clinical features and cytogenetic features. We further discovered that overexpression of NEAT1 was associated with Dex resistance and a poor prognosis in MM patients. CONCLUSION: LncRNA NEAT1 has a significant value that might act as a promoting factor in the development of MM and may be severed as a diagnostic factor in MM. NEAT1 invovled in Dex resistance, which provide a new interpretation during the chemotherapy for MM.

Hepatocellular carcinoma (HCC) is common worldwide, and novel therapeutic targets and biomarkers are needed to improve outcomes. In this study, bioinformatics analyses combined with in vitro and in vivo assays were used to identify the potential therapeutic targets. Differentially expressed genes (DEG) in HCC were identified by the intersection between The Cancer Genome Atlas and International Cancer Genome Consortium data. The DEGs were evaluated by a gene set enrichment analysis as well as Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. A protein interaction network, univariate Cox regression, and Lasso regression were used to screen out hub genes correlated with survival. Increased expression of the long noncoding RNA GBAP1 in HCC was confirmed in additional datasets and its biological function was evaluated in HCC cell lines and nude mice. Among 121 DEGs, GBAP1 and PRC1 were identified as hub genes with significant prognostic value. Overexpression of GBAP1 in HCC was confirmed in 21 paired clinical tissues and liver cancer or normal cell lines. The inhibition of GBAP1 expression reduced HCC cell proliferation and promoted apoptosis by inactivating the PI3K/AKT pathway in vitro and in vivo. Therefore, GBAP1 has a pro-oncogenic function in HCC and is a candidate prognostic biomarker and therapeutic target.

BACKGROUND: Aromatase inhibitors (AI) are frequently used to treat hormone-receptor-positive breast cancer, but they have multiple adverse effects (e.g., osteoporosis, arthralgia), resulting in premature therapy discontinuation/switch. Physical activity (PA) can attenuate these negative effects and improve quality of life (QoL). However, most cancer survivors fail to perform/sustain adequate PA levels, especially in the long-term. Theory-based interventions, using evidence-based behavior change techniques, aimed at promoting long-term behavior change in breast cancer survivors are effective, but remain scarce and fail to promote self-regulatory skills and better-quality motivations associated with sustained PA adoption. This paper describes the design of the PAC-WOMAN trial, which will test the long-term effectiveness and cost-effectiveness of two state of the art, group-based interventions encouraging sustained changes in PA, sedentary behavior, and QoL. Additional aims include examining the impact of both interventions on secondary outcomes (e.g., body composition, physical function), and key moderators/mediators of short and long-term changes in primary outcomes. METHODS: A 3-arm pragmatic randomized controlled trial, involving a 4-month intervention and a 12-month follow-up, will be implemented, in a real exercise setting, to compare: 1) brief PA counseling/motivational intervention; 2) structured exercise program vs. waiting-list control group. Study recruitment goal is 122 hormone-receptor-positive breast cancer survivors (stage I-III), on AI therapy (post-primary treatment completion) ≥ 1 month, ECOG 0-1. Outcome measures will be obtained at baseline, 4 months (i.e., post-intervention), 10 and 16 months. Process evaluation, analyzing implementation determinants, will also be conducted. DISCUSSION: PAC-WOMAN is expected to have a relevant impact on participants PA and QoL and provide insights for the improvement of interventions designed to promote sustained adherence to active lifestyle behaviors, facilitating its translation to community settings. TRIAL REGISTRATION: April 20, 2023 - NCT05860621. April 21, 2023 - https://doi.org/10.17605/OSF.IO/ZAQ9N April 27, 2023 - UMIN000050945.

BACKGROUND: The COVID-19 pandemic has affected all aspects of the healthcare system, including prevention, treatment, rehabilitation of diseases and health education; access to essential therapies; allocation of finance & facilities to health issues, and governance of diseases, including COVID-19 and other diseases. Consequently, the burden of COVID-19 was not only attributable to the multiorgan involvement and detailed presentation of the disease but also to the inadequate management of other diseases resulting from the exclusive allocation of resources and medical personnel to the pandemic crisis. Over the mentioned period, one observed deficiency was the lack of public and official favor for conventional screening protocols. To this end, this study aims to evaluate the impact of the COVID-19 pandemic on colorectal cancer (CRC) screening protocols at Shahid Beheshti University of Medical Sciences in Tehran, Iran, in an effort to identify individuals at risk for CRC and provide them with intensive screening and therapy. METHODS: This is an observational study comparing the number of candidates for CRC screening referred to primary, secondary, and tertiary health-care centers under supervision of Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran in a 2-year interval before and after COVID-19 pandemics. Patients with intermediate- and high-risk criteria for colorectal cancer were included in the study and were screened by fecal immunochemical test. Patients with positive or indeterminate fecal test results were further evaluated with colonoscopy in research institute for gastroenterology and liver diseases where is a tertiary referral center for CRC screening. Finally, the decrease percentage of screening tests and endoscopic findings during the pandemic period compared to pre-pandemic period was calculated and interpreted. RESULTS: A significant decrease in the number of performed fecal immunochemical tests (FITs), referred positive FITs, and referred patients with positive alarm signs to the Research Institute of Gastroenterology and Liver Diseases (RIGLD) center inevitably led to a considerable decrease in the number of endoscopic findings, including high-risk adenomas, sessile serrated polyps, and even early-stage colorectal cancers (CRCs). CONCLUSION: The disruption of screening protocols caused by the COVID-19 pandemic appears to increase the number of patients with high-grade and end-stage CRCs referred in the near future.

PURPOSE: Adjuvant endocrine treatment is essential for treating luminal subtypes of breast cancer, which constitute 75% of all breast malignancies. However, the detrimental side effects of treatment make it difficult for many patients to complete the guideline-required treatment. Such non-adherence may jeopardize the lifesaving ability of anti-estrogen therapy. In this systematic review, we aimed to assess the consequences of non-adherence and non-persistence from available studies meeting strict statistical and clinical criteria. METHODS: A systematic literature search was performed using several databases, yielding identification of 2,026 studies. After strict selection, 14 studies were eligible for systematic review. The review included studies that examined endocrine treatment non-adherence (patients not taking treatment as prescribed) or non-persistence (patients stopping treatment prematurely), in terms of the effects on event-free survival or overall survival among women with non-metastatic breast cancer. RESULTS: We identified 10 studies measuring the effects of endocrine treatment non-adherence and non-persistence on event-free survival. Of these studies, seven showed significantly poorer survival for the non-adherent or non-persistent patient groups, with hazard ratios (HRs) ranging from 1.39 (95% CI, 1.07 to 1.53) to 2.44 (95% CI, 1.89 to 3.14). We identified nine studies measuring the effects of endocrine treatment non-adherence and non-persistence on overall survival. Of these studies, seven demonstrated significantly reduced overall survival in the groups with non-adherence and non-persistence, with HRs ranging from 1.26 (95% CI, 1.11 to 1.43) to 2.18 (95% CI, 1.99 to 2.39). CONCLUSION: The present systematic review demonstrates that non-adherence and non-persistence to endocrine treatment negatively affect event-free and overall survival. Improved follow-up, with focus on adherence and persistence, is vital for improving health outcomes among patients with non-metastatic breast cancer.

BACKGROUND: CXC-chemokine receptor 2 (CXCR2) expression was found to be down-regulated on circulating monocytes of cancer patients. Here, we analyze the percentage of CD14+CXCR2+ monocyte subsets in hepatocellular carcinoma (HCC) patients, and investigate the mechanisms that regulate CXCR2 surface expression on monocytes and its biological function. METHODS: Flow cytometry was used to analyze the proportion of the CD14+CXCR2+ subset from the total circulating monocytes of HCC patients. Interleukin 8 (IL-8) levels were measured from serum and ascites, and their correlation with the CD14+CXCR2+ monocyte subset proportion was calculated. THP-1 cells were cultured in vitro and treated with recombinant human IL-8 and CXCR2 surface expression was analyzed. CXCR2 was knocked down to examine how it affects the antitumor activity of monocytes. Finally, a monoacylglycerol lipase (MAGL) inhibitor was added to analyze its effect on CXCR2 expression. RESULTS: A decrease in the proportion of the CD14+CXCR2+ monocyte subset was observed in HCC patients compared with healthy controls. CXCR2+ monocyte subset proportion was associated with the AFP value, TNM stage, and liver function. Overexpression of IL-8 was observed in the serum and ascites of HCC patients, and negatively correlated with CXCR2+ monocyte proportion. IL-8 decreased CXCR2 expression in THP-1 cells, contributing to decreased antitumor activity toward HCC cells. MAGL expression in THP-1 cells was up-regulated after IL-8 treatment, and the MAGL inhibitor partially reversed the effects of IL-8 on CXCR2 expression. CONCLUSIONS: Overexpression of IL-8 drives CXCR2 down-regulation on circulating monocytes of HCC patients, which could be partially reversed by a MAGL inhibitor.

BACKGROUND: Cancer is highly prevalent worldwide. Family resilience is a positive variable that helps families burdened by advanced cancer to cope effectively. This study aimed to describe the family resilience of advanced cancer patients and caregivers in dyads and identify its influencing factors at the individual and dyadic levels. METHODS: This multisite cross-sectional study was conducted in oncology units in five tertiary hospitals in China. A total of 270 advanced cancer patient-caregiver dyads were recruited between June 2020 and March 2021. Patients' and caregivers' family resilience was measured by the Family Resilience Assessment Scale. Data on potential influencing factors, including demographic and disease-related characteristics as well as family sense of coherence, psychological resilience, perceived social support, symptom burden, and caregiver burden, were collected. Multilevel modeling analysis was adopted to control for the interdependence of the dyads. RESULTS: A total of 241 dyads were included in the data analysis. The mean ages of patients and caregivers were 53.96 (SD 15.37) and 45.18 (SD 13.79) years, respectively. Most caregivers were spouses and adult children (45.6% and 39.0%, respectively). Patients reported a higher mean family resilience score than caregivers (152.56 vs. 149.87, respectively). Undergoing fewer than two types of treatment and a lower symptom burden of patients predicted higher patient (B = -9.702, -0.134, respectively) and caregiver (B = -5.462, -0.096, respectively) family resilience. Patients also reported higher family resilience under the following conditions: 1) were on a medical insurance plan other than the new rural cooperative medical system (B = 6.089), 2) had a better family sense of coherence (B = 0.415), 3) whose caregivers were unmarried (B = 8.618), perceived lower social support (B = -0.145) and higher psychological resilience (B = 0.313). Caregivers who were ≤ 44 years old (B = -3.221), had similar previous caregiving experience (B = 7.706), and had a stronger family sense of coherence (B = 0.391) reported higher family resilience. CONCLUSIONS: Our findings highlight the importance of adopting a dyadic approach when caring for advanced cancer patients and their caregivers. Dyadic longitudinal research is suggested to discover more modifiable factors of family resilience and tailored interventions are needed to obtain optimal dyadic outcomes.

BACKGROUND: Lymph node metastasis (LNM) is an important factor affecting endometrial cancer (EC) prognosis. Current controversy exists as to how to accurately assess the risk of lymphatic metastasis. Metabolic syndrome has been considered a risk factor for endometrial cancer, yet its effect on LNM remains elusive. We developed a nomogram integrating metabolic syndrome indicators with other crucial variables to predict lymph node metastasis in endometrial cancer. METHODS: This study is based on patients diagnosed with EC in Peking University People's Hospital between January 2004 and December 2020. A total of 1076 patients diagnosed with EC and who underwent staging surgery were divided into training and validation cohorts according to the ratio of 2:1. Univariate and multivariate logistic regression analyses were used to determine the significant predictive factors. RESULTS: The prediction nomogram included MSR, positive peritoneal cytology, lymph vascular space invasion, endometrioid histological type, tumor size >  = 2 cm, myometrial invasion >  = 50%, cervical stromal invasion, and tumor grade. In the training group, the area under the curve (AUC) of the nomogram and Mayo criteria were 0.85 (95% CI: 0.81-0.90) and 0.77 (95% CI: 0.77-0.83), respectively (P < 0.01). In the validation group (N = 359), the AUC was 0.87 (95% CI: 0.82-0.93) and 0.80 (95% CI: 0.74-0.87) for the nomogram and the Mayo criteria, respectively (P = 0.01). Calibration plots revealed the satisfactory performance of the nomogram. Decision curve analysis showed a positive net benefit of this nomogram, which indicated clinical value. CONCLUSION: This model may promote risk stratification and individualized treatment, thus improving the prognosis.

BACKGROUND: Locally advanced pancreatic ductal adenocarcinoma (PDAC), accounting for about 30% of PDAC patients, is difficult to cure by radical resection or systemic chemotherapy alone. A multidisciplinary strategy is required and our TT-LAP trial aims to evaluate whether triple-modal treatment with proton beam therapy (PBT), hyperthermia, and gemcitabine plus nab-paclitaxel is a safe and synergistically effective treatment for patients with locally advanced PDAC. METHODS: This trial is an interventional, open-label, non-randomized, single-center, single-arm phase I/II clinical trial organized and sponsored by the University of Tsukuba. Eligible patients who are diagnosed with locally advanced pancreatic cancer, including both borderline resectable (BR) and unresectable locally advanced (UR-LA) patients, and selected according to the inclusion and exclusion criteria will receive triple-modal treatment consisting of chemotherapy, hyperthermia, and proton beam radiation. Treatment induction will include 2 cycles of chemotherapy (gemcitabine plus nab-paclitaxel), proton beam therapy, and 6 total sessions of hyperthermia therapy. The initial 5 patients will move to phase II after adverse events are verified by a monitoring committee and safety is ensured. The primary endpoint is 2-year survival rate while secondary endpoints include adverse event rate, treatment completion rate, response rate, progression-free survival, overall survival, resection rate, pathologic response rate, and R0 (no pathologic cancer remnants) rate. The target sample size is set at 30 cases. DISCUSSION: The TT-LAP trial is the first to evaluate the safety and effectiveness (phases1/2) of triple-modal treatment comprised of proton beam therapy, hyperthermia, and gemcitabine/nab-paclitaxel for locally advanced pancreatic cancer. ETHICS AND DISSEMINATION: This protocol was approved by the Tsukuba University Clinical Research Review Board (reference number TCRB22-007). Results will be analyzed after study recruitment and follow-up are completed. Results will be presented at international meetings of interest in pancreatic cancer plus gastrointestinal, hepatobiliary, and pancreatic surgeries and published in peer-reviewed journals. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs031220160. Registered 24 th June 2022, https://jrct.niph.go.jp/en-latest-detail/jRCTs031220160 .

BACKGROUND: Sensitive and reproducible detection of residual disease after treatment is a major challenge for patients with locally advanced head and neck cancer. Indeed, the current imaging techniques are not always reliable enough to determine the presence of residual disease. The aim of the NeckTAR trial is to assess the ability of circulating DNA (cDNA), both tumoral and viral, at three months post-treatment, to predict residual disease, at the time of the neck dissection, among patients with partial cervical lymph node response on PET-CT, after potentiated radiotherapy. METHODS: This will be an interventional, multicentre, single-arm, open-label, prospective study. A blood sample will be screened for cDNA before potentiated radiotherapy and after 3 months if adenomegaly persists on the CT scan 3 months after the end of treatment. Patients will be enrolled in 4 sites in France. Evaluable patients, i.e. those with presence of cDNA at inclusion, an indication for neck dissection, and a blood sample at M3, will be followed for 30 months. Thirty-two evaluable patients are expected to be recruited in the study. DISCUSSION: The decision to perform neck dissection in case of persistent cervical adenopathy after radio-chemotherapy for locally advanced head and neck cancer is not always straightforward. Although studies have shown that circulating tumour DNA is detectable in a large proportion of patients with head and neck cancer, enabling the monitoring of response, the current data is insufficient to allow routine use of this marker. Our study could lead to better identification of patients who do not have residual lymph node disease in order to avoid neck dissection and preserve their quality-of-life while maintaining their prospects of survival. TRIAL REGISTRATION: Clinicaltrials.gov: NCT05710679, registered on 02/02/2023, https://clinicaltrials.gov/ct2/show/ . Identifier with the French National Agency for the Safety of Medicines and Health Products (ANSM): N°ID RCB 2022-A01668-35, registered on July 15th, 2022.

BACKGROUND: Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU)/levo-leucovorin (Levo-LV) was approved for unresectable pancreatic cancer (UR-PC) in March 2020 in Japan. Levo-LV is administered by intravenous infusion over 120 min following 90 min intravenous infusion of nal-IRI (conventional method), causing a significant burden on both patients and the outpatient chemotherapy room owing to the prolonged administration time. Thus, from July 2021, we introduced the simultaneous intravenous administration of nal-IRI and Levo-LV (parallel method) with the approval of the institutional regimen committee. METHODS: We retrospectively reviewed the data of 69 patients with UR-PC who received nal-IRI plus 5-FU/Levo-LV at our hospital between June 2020 and October 2021. We examined the safety of the parallel method and compared the treatment outcomes and administration times between the two methods. RESULTS: The median age was 66 years (54%, male). Disease statuses were locally advanced, metastatic, and postoperative recurrence after pancreatectomy in 7, 50, and 12 patients, respectively. Nal-IRI plus 5-FU/Levo-LV treatment was second and third-line or later in 35 and 34 patients, respectively. No intravenous line problems were observed during the parallel administration of nal-IRI and Levo-LV. Although there were no significant differences in response rates and adverse events between the two methods, the administration time was significantly shorter in the parallel method than in the conventional method. CONCLUSION: The parallel administration of nal-IRI and Levo-LV is clinically safe and not inferior in efficacy. Moreover, parallel administration may offer convenience to patients and healthcare workers by reducing administration time.

BACKGROUND: Glioblastoma (GBM), a malignant brain tumor, has poor survival outcomes due to recurrence or drug resistance. We found that SH3GLB1 is a crucial factor for cells to evade temozolomide (TMZ) cytotoxicity through autophagy-mediated oxidative phosphorylation, which is associated with CD133 levels. Therefore, we propose that SH3GLB1 participate in the impact on tumor-initiating cells (TICs). METHODS: The parental, the derived resistant cell lines and their CD133+ cells were used, and the levels of the proteins were compared by western blotting. Then RNA interference was applied to observe the effects of the target protein on TIC-related features. Finally, in vitro transcription assays were used to validate the association between SH3GLB1 and CD133. RESULTS: The CD133+ cells from resistant cells with enhanced SH3GLB1 levels more easily survived cytotoxic treatment than those from the parental cells. Inhibition of SH3GLB1 attenuated frequency and size of spheroid formation, and the levels of CD133 and histone 4 lysine 5 (H4K5) acetylation can be simultaneously regulated by SH3GLB1 modification. The H4K5 acetylation of the CD133 promoter was later suggested to be the mediating mechanism of SH3GLB1. CONCLUSIONS: These data indicate that SH3GLB1 can regulate CD133 expression, suggesting that the protein plays a crucial role in TICs. Our findings on the effects of SH3GLB1 on the cells will help explain tumor resistance formation.

BACKGROUND: Endometrial Cancer (EC) is one of the most prevalent malignancies that affect the female population globally. In the context of immunotherapy, Tumor Mutation Burden (TMB) in the DNA polymerase epsilon (POLE) subtype of this cancer holds promise as a viable therapeutic target. METHODS: We devised a method known as NEM-TIE to forecast the TMB status of patients with endometrial cancer. This approach utilized a combination of the Network Evolution Model, Transfer Information Entropy, Clique Percolation (CP) methodology, and Support Vector Machine (SVM) classification. To construct the Network Evolution Model, we employed an adjacency matrix that utilized transfer information entropy to assess the information gain between nodes of radiomic-clinical features. Subsequently, using the CP algorithm, we unearthed potentially pivotal modules in the Network Evolution Model. Finally, the SVM classifier extracted essential features from the module set. RESULTS: Upon analyzing the importance of modules, we discovered that the dependence count energy in tumor volumes-of-interest holds immense significance in distinguishing TMB statuses among patients with endometrial cancer. Using the 13 radiomic-clinical features extracted via NEM-TIE, we demonstrated that the area under the receiver operating characteristic curve (AUROC) in the test set is 0.98 (95% confidence interval: 0.95-1.00), surpassing the performance of existing techniques such as the mRMR and Laplacian methods. CONCLUSIONS: Our study proposed the NEM-TIE method as a means to identify the TMB status of patients with endometrial cancer. The integration of radiomic-clinical data utilizing the NEM-TIE method may offer a novel technology for supplementary diagnosis.

BACKGROUND: Radical resection plus lymph node dissection is a common treatment for patients with T1-3N0M0 non-small cell lung cancer (NSCLC). Few models predicted the survival outcomes of these patients. This study aimed to developed a nomogram for predicting their overall survival (OS). MATERIALS AND METHODS: This study involved 3002 patients with T1-3N0M0 NSCLC after curative resection between January 1999 and October 2013. 1525 Patients from Sun Yat-sen University Cancer Center were randomly allocated to training cohort and internal validation cohort in a ratio of 7:3. 1477 patients from ten institutions were recruited as external validation cohort. A nomogram was constructed based on the training cohort and validated by internal and external validation cohort to predict the OS of these patients. The accuracy and practicability were tested by Harrell's C-indexes, calibration plots and decision curve analyses (DCA). RESULTS: Age, sex, histological classification, pathological T stage, and HI standard were independent factors for OS and were included in our nomogram. The C-index of the nomogram for OS estimates were 0.671 (95% CI, 0.637-0.705),0.632 (95% CI, 0.581-0.683), and 0.645 (95% CI, 0.617-0.673) in the training cohorts, internal validation cohorts, and external validation cohort, respectively. The calibration plots and DCA for predictions of OS were in excellent agreement. An online version of the nomogram was built for convenient clinical practice. CONCLUSIONS: Our nomogram can predict the OS of patients with T1-3N0M0 NSCLC after curative resection. The online version of our nomogram offer opportunities for fast personalized risk stratification and prognosis prediction in clinical practice.

BACKGROUND: Precise prognostication is the key to optimum and effective treatment planning for early-stage hormone receptor (HR) positive, HER2/neu negative breast cancer patients. Differences in the breast cancer incidence and tumor anatomical features at diagnosis, pharmacogenomics data between Western and Indian women along with the vast diversity in the economic status and differences in insurance policies of these regions; suggest recommendations put forward for Western women might not be applicable to Indian/Asian women. Opinions from oncologists through a voting survey on various prognostic factors/tools to be considered for planning adjuvant therapy are consolidated in this report for the benefit of oncologists of the sub-continent, SAARC and Asia's LMIC (low and middle-income countries). METHODS: A three-phase DELPHI survey was conducted to collect opinions on prognostic factors considered for planning adjuvant therapy in early-stage HR+/HER2/neu negative breast cancer patients. A panel of 25 oncologists with expertise in breast cancer participated in the survey conducted in 2021. The experts provided opinions as 'agree' or disagree' or 'not sure' in phases-1 and 2 which were conducted virtually; in the final phase-3, all the panel experts met in person and concluded the survey. RESULTS: Opinions on 41 statements related to prognostic factors/tools and their implications in planning adjuvant endocrine/chemotherapy were collected. All the statements were supported by the latest data from the clinical trials (prospective/retrospective). The statements with opinions of consensus less than 66% were disseminated in phase-2, and later in phase-3 with supporting literature. In phase-3, all the opinions from panelists were consolidated and guidelines were framed. CONCLUSIONS: This consensus guideline will assist oncologists of India, SAARC and LMIC countries in informed clinical decision-making on adjuvant treatment in early HR+/HER2/neu negative breast cancer patients.

BACKGROUND: Circular RNAs (circRNAs), which are involved in various human malignancies, have emerged as promising biomarkers. The present study aimed to investigate unique expression profiles of circRNAs in hepatocellular carcinoma (HCC) and identify novel biomarkers associated with HCC development and progression. METHODS: CircRNA expression profiles of HCC tissues were jointly analyzed to identify differentially expressed circRNAs. Overexpression plasmid and siRNA targeting candidate circRNAs were used in functional assays in vitro. CircRNA-miRNA interactions were predicted using miRNAs expressed in the miRNA-seq dataset GSE76903. To further screen downstream genes targeted by the miRNAs, survival analysis and qRT-PCR were conducted to evaluate their prognostic role in HCC and construct a ceRNA regulatory network. RESULTS: Three significantly upregulated circRNAs, hsa_circ_0002003, hsa_circ_0002454, and hsa_circ_0001394, and one significantly downregulated circRNA, hsa_circ_0003239, were identified and validated by qRT-PCR. Our in vitro data indicated that upregulation of hsa_circ_0002003 accelerated cell growth and metastasis. Mechanistically, DTYMK, DAP3, and STMN1, which were targeted by hsa-miR-1343-3p, were significantly downregulated in HCC cells when hsa_circ_0002003 was silenced and were significantly correlated with poor prognosis in patients with HCC. CONCLUSION: Hsa_circ_0002003 may play critical roles in HCC pathogenesis and serve as a potential prognostic biomarker for HCC. Targeting the hsa_circ_0002003/hsa-miR-1343-3p/STMN1 regulatory axis could be an effective therapeutic strategy in patients with HCC.

BACKGROUND: Whole-genome doubling (WGD) is a common mutation in cancer. Various studies have suggested that WGD is associated with a poor prognosis in cancer. However, the detailed association between WGD occurrence and prognosis remains unclear. In this study, we aimed to elucidate the mechanism by which WGD affects prognosis using sequencing data from the Pan-Cancer Analysis of Whole Genomes (PCAWG) and The Cancer Genome Atlas. METHODS: Whole-genome sequencing data of 23 cancer types were downloaded from PCAWG project. We defined the WGD event in each sample using the WGD status annotated using PCAWG. We used MutationTimeR to predict the relative timings of mutations and loss of heterozygosity (LOH) in WGD, thus evaluating their association with WGD. We also analyzed the association between WGD-associated factors and patient prognosis. RESULTS: WGD was associated with several factors, e.g., length of LOH regions. Survival analysis using WGD-associated factors revealed that longer LOH regions and LOH in chr17 were associated with poor prognosis in samples with WGD (WGD samples) and samples without WGD (nWGD samples). In addition to these two factors, nWGD samples showed that the number of mutations in tumor suppressor genes was associated with prognosis. Moreover, we explored the genes associated with prognosis in both samples separately. CONCLUSION: The prognosis-related factors in WGD samples differed significantly compared with those in nWGD samples. This study emphasizes the need for different treatment strategies for WGD and nWGD samples.

OBJECTIVE: To investigate the relationship among 18 heavy metals, microsatellite instability (MSI) status, ERCC1, XRCC1 (rs25487), BRAF V600E and 5 tumor markers and their role in the development of colorectal cancer (CRC). METHODS: A total of 101 CRC patients and 60 healthy controls were recruited in the present study. The levels of 18 heavy metals were measured by ICP-MS. MSI status and the genetic polymorphism were determined by PCR (FP205-02, Tiangen Biochemical Technology Co., Ltd., Beijing, China) and Sanger sequencing. Spearman's rank correlation was used to analyze the relationship among various factors. RESULTS: The level of selenium (Se) was lower in the CRC group compared with the control group (p < 0.01), while vanadium (V), arsenic (As), tin (Sn), barium (Ba) and lead (Pb) were higher (p < 0.05), chromium (Cr) and copper (Cu) were significantly higher (p < 0.0001) in the CRC group than those in the control group. Multivariate logistic regression analysis indicated that Cr, Cu, As and Ba were the risk factors for CRC. In addition, CRC was positively correlated with V, Cr, Cu, As, Sn, Ba and Pb, but negatively correlated with Se. MSI was positively correlated with BRAF V600E, but negatively correlated with ERCC1. BRAF V600E was positively correlated with antimony (Sb), thallium (Tl), CA19-9, NSE, AFP and CK19. XRCC1 (rs25487) was found to be positively correlated with Se but negatively correlated with Co. The levels of Sb and Tl were significantly higher in the BRAF V600E positive group compared to the negative group. The mRNA expression level of ERCC1 was significantly higher (P = 0.035) in MSS compared to MSI. And there was a significant correlation between XRCC1 (rs25487) polymorphism and MSI status (P<0.05). CONCLUSION: The results showed that low level of Se and high levels of V, As, Sn, Ba, Pb, Cr, and Cu increased the risk of CRC. Sb and Tl may cause BRAF V600E mutations, leading to MSI. XRCC1 (rs25487) was positively correlated with Se but negatively correlated with Co. The expression of ERCC1 may be related to MSS, while the XRCC1 (rs25487) polymorphism is related to MSI.

BACKGROUND: Insulin resistance is an overlapping risk factor for both heart and breast cancer, while its interaction with cardiotoxicity in breast cancer (BC) patients is not clear. This study investigated the impact of insulin resistance on cardiac remodeling in patients with human epidermal growth factor receptor 2 (HER2)-positive BC during and after trastuzumab therapy in real-world clinical practice. METHODS: HER2-positive BC patients who received trastuzumab treatment between December 2012 and December 2017 were reviewed and 441 patients with baseline metabolic indices and serial echocardiographic measurements (baseline, 6, 12, and 18 months) after trastuzumab therapy initiation were included. Repeated measurement analysis of variance was used to evaluate temporal trends in multiparameter echocardiography. Linear mixed model was applied to further evaluate the role of insulin resistance in forementioned changes. Correlation of homeostasis model assessment-estimated insulin resistance (HOMA-IR) and triglyceride-glucose index (TyG) levels to changes in echocardiography parameters was explored. RESULTS: Of 441 patients (mean age 54 ± 10 [SD] years), 61.8% received anthracycline-based chemotherapy, 33.5% received left-sided radiotherapy, 46% received endocrine therapy. No symptomatic cardiac dysfunction was observed over the therapy course. A total of 19 (4.3%) participants experienced asymptomatic cancer therapy-related cardiac dysfunction (CTRCD), and the peak onset time was 12 months after the initiation of trastuzumab. Albeit relatively low CTRCD incidence, cardiac geometry remodeling, especially left atrial (LA) dilation over therapy was notable and was more severe in high HOMA-IR and TyG level groups (P < 0.01). Noteworthy, a partial reversibility of cardiac remodeling was observed with treatment cessation. Additionally, HOMA-IR level positively correlated to changes in LA diameter from baseline to 12 months (r = 0.178, P = 0.003). No significant association (all P > 0.10) was detected between HOMA-IR or TyG level and dynamic left ventricular parameter evaluation. Multivariate linear regression analysis demonstrated that higher HOMA-IR level was an independent determinant for LA enlargement in BC patients during anti-HER2 targeted therapy course after adjusting for confounding risk factors (P = 0.006). CONCLUSION: Insulin resistance was associated with left atrial adverse remodeling (LAAR) in HER2-positive BC patients that received standard trastuzumab therapy, indicating that insulin resistance could be a supplementation to baseline cardiovascular risk stratification proforma for HER2-targeted antitumor therapies.

BACKGROUND: The prognosis of patients with colorectal cancer is related to early detection. However, commonly used screening markers lack sensitivity and specificity. In this study, we identified diagnostic methylation sites for colorectal cancer. METHODS: After screening the colorectal cancer methylation dataset, diagnostic sites were identified via survival analysis, difference analysis, and ridge regression dimensionality reduction. The correlation between the selected methylation sites and the estimation of immune cell infiltration was analyzed. The accuracy of the diagnosis was verified using different datasets and the 10-fold crossover method. RESULTS: According to Gene Ontology, the main enrichment pathways of genes with hypermethylation sites are axon development, axonogenesis, and pattern specification processes. However, the Kyoto Encyclopedia of Genes and Genomes (KEGG) suggests the following main enrichment pathways: neuroactive ligand-receptor interaction, calcium signaling, and cAMP signaling. In The Cancer Genome Atlas (TCGA) and GSE131013 datasets, the area under the curve of cg07628404 was > 0.95. For the NaiveBayes machine model of cg02604524, cg07628404, and cg27364741, the accuracies of 10-fold cross-validation in the GSE131013 and TCGA datasets were 95% and 99.4%, respectively. The survival prognosis of the hypomethylated group (cg02604524, cg07628404, and cg27364741) was better than that of the hypermethylated group. The mutation risk did not differ between the hypermethylated and hypomethylated groups. The correlation coefficient between the three loci and CD4 central memory T cells, hematological stem cells, and other immune cells was not high (p < 0.05). CONCLUSION: In cases of colorectal cancer, the main enrichment pathway of genes with hypermethylated sites was axon and nerve development. In the biopsy tissues, the hypermethylation sites were diagnostic for colorectal cancer, and the NaiveBayes machine model of the three loci showed good diagnostic performance. Site (cg02604524, cg07628404, and cg27364741) hypermethylation predicts poor survival for colorectal cancer. Three methylation sites were weakly correlated with individual immune cell infiltration. Hypermethylation sites may be a useful repository for diagnosing colorectal cancer.

BACKGROUND: Ovarian clear cell carcinomas (OCCCs) are rare, aggressive and chemoresistant tumors. Geographical and ethnic differences in the incidence of OCCC have been reported with a higher incidence in Asiatic countries. There is a paucity of information regarding OCCC in Latin America (LA) and other countries. METHODS: Here, we characterized two cohorts of 33 patients with OCCC from LA (24 from Brazil and 9 from Costa Rica) and a cohort of 27 patients from Spain. Genomic analysis was performed for 26 OCCC using the OncoScan platform. Tumors were classified according to their genomic landscapes into subgroups. Clinical parameters were related to the frequency of genomic aberrations. RESULTS: The median overall survival (OS) was not significantly different between the cohorts. Genomic landscapes were characterized by different homologous recombination deficiency (HRD) levels. No difference in the distribution of genomic landscapes profiles was detected between patients from the different cohorts. OCCCs with MYC-amplified tumors harboring a concomitant loss of a region in chromosome 13q12-q13 that includes the BRCA2 gene had the longest OS. In contrast, patients carrying a high number (> 30) of total copy number (CN) aberrations with no concomitant alterations in MYC and BRCA2 genes presented the shortest OS. Furthermore, amplification of the ASH1L gene was also associated with a shorter OS. Initial-stage OCCCs with early progression were characterized by gains in the JNK1 and MKL1 genes. CONCLUSIONS: Our results provide new data from understudied OCCC populations and reveal new potential markers for OCCCs.

BACKGROUND: Small extracellular vesicles (sEVs) have great potential as new biomarkers in liquid biopsy. However, due to the limitations of sEVs extraction and component analysis procedures, further clinical applications of sEVs are hampered. Carcinoembryonic antigen (CEA) is a commonly used broad-spectrum tumor marker that is strongly expressed in a variety of malignancies. RESULTS: In this study, CEA+ sEVs were directly separated from serum using immunomagnetic beads, and the nucleic acid to protein ultraviolet absorption ratio (NPr) of CEA+ sEVs was determined. It was found that the NPr of CEA+ sEVs in tumor group was higher than that of healthy group. We further analyzed the sEV-derived nucleic acid components using fluorescent staining and found that the concentration ratio of double-stranded DNA to protein (dsDPr) in CEA+ sEVs was also significantly different between the two groups, with a sensitivity of 100% and a specificity of 41.67% for the diagnosis of pan-cancer. The AUC of dsDPr combined with NPr was 0.87 and the ACU of dsDPr combined with CA242 could reach 0.94, showing good diagnostic performance for pan-cancer. CONCLUSIONS: This study demonstrates that the dsDPr of CEA+ sEVs can effectively distinguish sEVs derived from tumor patients and healthy individuals, which can be employed as a simple and cost-effective non-invasive screening technology to assist tumor diagnosis.

BACKGROUND: Metabolic derangements and systemic inflammation are related to the progression of colorectal cancer (CRC) and the prognoses of these patients. The survival of stage II and III CRC patients existed considerable heterogeneity highlighting the urgent need for new prediction models. This study aimed to develop and validate prognostic nomograms based on preoperative serum liver enzyme as well as evaluate the clinical utility. METHODS: A total of 4014 stage II/III primary CRC patients pathologically diagnosed from January 2007 to December 2013 were included in this study. These patients were randomly divided into a training set (n = 2409) and a testing set (n = 1605). Univariate and multivariate Cox analyses were used to select the independent factors for predicting overall survival (OS) and disease-free survival (DFS) of stage II/III CRC patients. Next, nomograms were constructed and validated to predict the OS and DFS of individual CRC patients. The clinical utility of nomograms, tumor-node-metastasis (TNM), and the American Joint Committee on Cancer (AJCC) system was evaluated using time-dependent ROC and decision curve analyses. RESULTS: Among seven preoperative serum liver enzyme markers, aspartate aminotransferase-to-alanine aminotransferase ratio (De Ritis ratio) was identified as an independent factor for predicting both OS and DFS of stage II/III CRC patients. The nomograms incorporated De Ritis ratio and significant clinicopathological features achieved good accuracy in terms of OS and DFS prediction, with C-index of 0.715 and 0.692, respectively. The calibration curve showed good agreement between prediction by nomogram and actual observation. The results of time-dependent ROC and decision curve analyses suggested that the nomograms had improved discrimination and greater clinical benefits compared with TNM and AJCC staging. CONCLUSIONS: De Ritis ratio was an independent predictor in predicting both the OS and DFS of patients with stage II/III CRC. Nomograms based on De Ritis ratio and clinicopathological features showed better clinical utility, which is expected to help clinicians develop appropriate individual treatment strategies for patients with stage II /III CRC.

BACKGROUND: Gene fusions are important cancer drivers in pediatric cancer and their accurate detection is essential for diagnosis and treatment. Clinical decision-making requires high confidence and precision of detection. Recent developments show RNA sequencing (RNA-seq) is promising for genome-wide detection of fusion products but hindered by many false positives that require extensive manual curation and impede discovery of pathogenic fusions. METHODS: We developed Fusion-sq to overcome existing disadvantages of detecting gene fusions. Fusion-sq integrates and "fuses" evidence from RNA-seq and whole genome sequencing (WGS) using intron-exon gene structure to identify tumor-specific protein coding gene fusions. Fusion-sq was then applied to the data generated from a pediatric pan-cancer cohort of 128 patients by WGS and RNA sequencing. RESULTS: In a pediatric pan-cancer cohort of 128 patients, we identified 155 high confidence tumor-specific gene fusions and their underlying structural variants (SVs). This includes all clinically relevant fusions known to be present in this cohort (30 patients). Fusion-sq distinguishes healthy-occurring from tumor-specific fusions and resolves fusions in amplified regions and copy number unstable genomes. A high gene fusion burden is associated with copy number instability. We identified 27 potentially pathogenic fusions involving oncogenes or tumor-suppressor genes characterized by underlying SVs, in some cases leading to expression changes indicative of activating or disruptive effects. CONCLUSIONS: Our results indicate how clinically relevant and potentially pathogenic gene fusions can be identified and their functional effects investigated by combining WGS and RNA-seq. Integrating RNA fusion predictions with underlying SVs advances fusion detection beyond extensive manual filtering. Taken together, we developed a method for identifying candidate gene fusions that is suitable for precision oncology applications. Our method provides multi-omics evidence for assessing the pathogenicity of tumor-specific gene fusions for future clinical decision making.

BACKGROUND: Several cancer immunotherapies that target the PD-L1/PD-1 pathway show promising clinical activity in patients with hepatocellular carcinoma (HCC). However, the standard of care in first-line treatment with atezolizumab (anti-PD-L1 therapy) in combination with bevacizumab is associated with a limited objective response rate. Telomerase reverse transcriptase (TERT) activation meets the criteria of oncogenic addiction in HCC and could be actionable therapeutic target and a relevant tumor antigen. Therefore we hypothesized that combining anti-PD-1/PD-L1 therapy with an anti-telomerase vaccine might be an attractive therapy in HCC. UCPVax is a therapeutic cancer vaccine composed of two separate peptides derived from telomerase (human TERT). UCPVax has been evaluated in a multicenter phase I/II study in non-small cell lung cancers and has demonstrated to be safe and immunogenic, and is under evaluation in combination with atezolizumab in a phase II clinical trial in tumors where telomerase reactivation contributes to an oncogene addiction (HPV+ cancers). The aim of the TERTIO study is to determine the clinical interest and immunological efficacy of a treatment combining the CD4 helper T-inducer cancer anti-telomerase vaccine (UCPVax) with atezolizumab and bevacizumab in unresectable HCC in a multicenter randomized phase II study. METHODS: Patients with locally advanced, metastatic or unresectable HCC who have not previously received systemic anti-cancer treatment are eligible. The primary end point is the objective response rate at 6 months. Patients will be allocated to a treatment arm with a randomization 2:1. In both arms, patients will receive atezolizumab at fixed dose of 1200 mg IV infusion and bevacizumab at fixed dose of 15 mg/kg IV infusion, every 3 weeks, according to the standard of care. In the experimental arm, these treatments will be combined with the UCPVax vaccine at 0.5 mg subcutaneously. DISCUSSION: Combining anti-PD-1/PD-L1 therapy with an anti-telomerase vaccine gains serious consideration in HCC, in order to extend the clinical efficacy of anti-PD-1/PD-L1. Indeed, anti-cancer vaccines can induce tumor-specific T cell expansion and activation and therefore restore the cancer-immunity cycle in patients lacking pre-existing anti-tumor responses. Thus, there is a strong rational to combine immune checkpoint blockade therapy and anticancer vaccine (UCPVax) in order to activate antitumor T cell immunity and bypass the immunosuppression in the tumor microenvironment in HCC. This pivotal proof of concept study will evaluate the efficacy and safety of the combination of a CD4 Th1-inducer cancer vaccine derived from telomerase (UCPVax) and atezolizumab plus bevacizumab in unresectable HCC, as well as confirming their synergic mechanism, and settling the basis for a new combination for future clinical trials. TRIAL REGISTRATION: NCT05528952.

BACKGROUND: The brain is a common site for cancer metastases. In case of large and/or symptomatic brain metastases, neurosurgical resection is performed. Adjuvant radiotherapy is a standard procedure to minimize the risk of local recurrence and is increasingly performed as local stereotactic radiotherapy to the resection cavity. Both hypofractionated stereotactic radiotherapy (HFSRT) and single fraction stereotactic radiosurgery (SRS) can be applied in this case. Although adjuvant stereotactic radiotherapy to the resection cavity is widely used in clinical routine and recommended in international guidelines, the optimal fractionation scheme still remains unclear. The SATURNUS trial prospectively compares adjuvant HFSRT with SRS and seeks to detect the superiority of HFSRT over SRS in terms of local tumor control. METHODS: In this single center two-armed randomized phase III trial, adjuvant radiotherapy to the resection cavity of brain metastases with HFSRT (6 - 7 × 5 Gy prescribed to the surrounding isodose) is compared to SRS (1 × 12-20 Gy prescribed to the surrounding isodose). Patients are randomized 1:1 into the two different treatment arms. The primary endpoint of the trial is local control at the resected site at 12 months. The trial is based on the hypothesis that HFSRT is superior to SRS in terms of local tumor control. DISCUSSION: Although adjuvant stereotactic radiotherapy after resection of brain metastases is considered standard of care treatment, there is a need for further prospective research to determine the optimal fractionation scheme. To the best of our knowledge, the SATURNUS study is the only randomized phase III study comparing different regimes of postoperative stereotactic radiotherapy to the resection cavity adequately powered to detect the superiority of HFSRT regarding local control. TRIAL REGISTRATION: The study was retrospectively registered with ClinicalTrials.gov, number NCT05160818, on December 16, 2021. The trial registry record is available on  https://clinicaltrials.gov/study/NCT05160818 . The presented protocol refers to version V1.3 from March 21, 2021.

BACKGROUND: IL-33 is a multifunctional cytokine with dual functions. However, the clinicopathological and prognostic significance of IL-33 in cancer patients, especially in patients with hepatocellular carcinoma (HCC), remains controversial. Therefore, we conducted a study of 565 patients with HCC and 561 healthy controls and performed a meta-analysis to quantitatively evaluate the above problems. METHODS: We collected blood from 565 patients with HCC and 561 healthy controls. ELISA was used to detect the concentrations of IL-33 and ST2 in the serum, and RT‒PCR was used to detect the levels of IL-33 and ST2 mRNA. Meanwhile, we collected comprehensive literature on IL-33 and the clinical characteristics of cancer patients retrieved from the PubMed, Web of Science and CNKI databases as of December 2022. An odds ratio (OR) with a 95% confidence interval (CI) was used to estimate the impact through overall and stratified analyses. RESULTS: Compared with the healthy control group, the levels of ST2 mRNA and serum in the peripheral blood of HCC patients increased (p < 0.05), while the levels of IL-33 mRNA and serum showed no significant difference between the two groups (p > 0.05). In the meta-analysis section, at the tissue level, the overall analysis showed that the expression of IL-33 was positively correlated with tumor stage, histological grade, distant metastasis, and tumor size. Compared with patients with low IL-33 expression, the 3-year overall survival (OS) rate (OR = 3.467, p < 0.001) and 5-year OS rate (OR = 2.784, p < 0.001) of patients with high IL-33 expression were lower. At the serum expression level, the overall analysis showed that the expression of IL-33 increased the risk of cancer, and the serum level of IL-33 was positively correlated with tumor stage and vascular invasion. CONCLUSION: IL-33/ST2 is a useful predictive or prognostic biomarker in clinical evaluation and may be used as a potential therapeutic target, but much research is needed to verify this hypothesis.

BACKGROUND: Circulating tumor cells (CTCs) have been a non-invasive technique which allows investigation of tumor characteristics. The purpose of this study was to investigate the relationship between circulating tumor cells and colorectal cancer. METHODS: The clinical data of 617 patients with colorectal cancer from October 2019 to March 2022 were retrospectively collected to analyze the correlation between CTCs and clinicopathologic characteristics. RESULTS: The CTCs value increased with the progression of Tumor(T) stage,Metastasis(M) stage and Tumor Node Metastasis(TNM) stage (P < 0.05), but not with Node (N) stage (P > 0.05). Binary logistic regression analysis showed that CTCs, CEA, CA125 and CA199 were independent risk factors for CRC metastasis. Compared with CTCs, CEA, CA125 and CA199, the Logistic model had the highest AUC (AUC = 0.778,95%CI: 0.732-0.824), and the specificity and sensitivity were 82.9% and 63.2%, respectively. After operation, chemo-radiotherapy and other treatment for CRC, CTCs and CEA were significantly decreased compared with before treatment (P < 0.05). In addition, Spearman Correlation showed significant correlation between CTCs and IgG (P = 0.000). CONCLUSION: CTCs, CEA, CA125 and CA199 were independent risk factors for CRC metastasis.CTCs can be used for the prediction of tumur metastasis, and the evaluation of therapeutic effect.

BACKGROUND: In breast cancer patients body image (BI) is a crucial aspect of quality of life (QoL). This study examined the postoperative impact of different surgical approaches on long-term BI analyzing real-world data to guide pre- and postoperative patient care and preserve QoL. METHODS: EORTC QLQ-BR23 BI scores were collected electronically in 325 breast cancer patients within routine clinical care for a duration of 41.5 months (11/17/2016 - 4/30/2020) at predefined time points preoperatively and repeatedly up to two years after breast-conserving surgery (BCS) (n = 212), mastectomy alone (M) (n = 27) or mastectomy with immediate breast reconstruction (MIBR) (n = 86). Higher scores indicated better BI. A linear mixed regression model was used to analyze the impact of BCS, M and MIBR, as well as non-surgical therapies on BI at treatment initiation and over time. RESULTS: BI scores deteriorated by 5 points (95%-confidence interval (CI) -8.94 to -1.57, p≈0.005) immediately after BCS, by 7 points (95%-CI -12.13 to -1.80, p≈0.008) after MIBR and by 19 points (95%-CI -27.34 to -10.34, p < 0.001) after M. The change over time after BCS (+ 0.10 points per week, 95%-CI -0.17 to 0.38), MIBR (-0.07 points per week, 95%-CI -0.35 to 0.20) and M (+ 0.14 points per week, 95%-CI -0.19 to 0.48) were not statistically significant (each p > 0.05). At treatment initiation chemotherapy was associated with a 22-point decline (95%-CI -25.39 to -17.87, p < 0.001) in BI score, while radiotherapy was associated with a 5-point increase (95%-CI 1.74 to 9.02, p≈0.004). However, over time chemotherapy was associated with a score recovery (+ 0.28 points per week, 95%-CI 0.19 to 0.37, p < 0.001), whereas for radiotherapy a trend towards BI deterioration was observed (-0.11 points per week, 95%-CI -0.23 to 0.02, p≈0.101). CONCLUSIONS: Breast cancer surgery negatively affects BI. BCS and MIBR presumably harm BI less than M in the early postoperative period. Our data suggests BI to be deteriorating in the long term after MIBR while improving after BCS or M. Radiotherapy seems to have an additional negative long-term impact on BI. These findings should be confirmed in further studies to enable evidence-based patient information as part of preoperative shared decision-making and postoperative patient care.

PURPOSE: This study examines prognostic value of preoperative serum bilirubin, including unconjugated bilirubin (UCB), conjugated bilirubin (CB), and total bilirubin (TB), in esophageal squamous cell carcinoma (ESCC) patients who underwent curative resection. METHODS: Between May 2010 and December 2012, a total of 351 ESCC patients were retrospectively reviewed. All the patients underwent curative resection as their primary treatment. Clinicopathological features and overall survival (OS) rate were investigated. Kaplan-Meier curves were used to calculate the OS rate, and the prognostic factors were identified by Cox regression model. Besides, the potential inhibition effect of UCB on ESCC was investigated with both in vitro and in vivo models. RESULTS: The higher-level groups of UCB, CB, and TB demonstrated longer OS than their low counterparts, with hazard ratio (HR) values of 0.567 (95% CI: 0.424-0.759), 0.698 (95% CI: 0.522-0.933), and 0.602 (95% CI: 0.449-0.807), respectively. All three forms of bilirubin were identified as independent prognostic factors for patients with ESCC, and they were found to effectively stratify the survival risk of patients at TNM stage III. In vivo and in vitro models further confirmed the inhibitory effect of unconjugated bilirubin (UCB) on the proliferation of ESCC. CONCLUSION: The findings of our study have shed new light on the prognostic value and biological functions of bilirubin in relation to ESCC. These results may contribute to a better understanding of the underlying mechanisms involved in ESCC tumorigenesis and provide potential therapeutic pathways for treating ESCC.

BACKGROUND: In this phase Ib/II open-label study, tumor immune suppression was targeted in patients with advanced refractory solid tumors and patients with recurrent/refractory non-small cell lung cancer (NSCLC) using galunisertib with nivolumab. METHODS: Eligible patients were ≥ 18 years old, had an Eastern Cooperative Oncology Group performance status ≤ 1, and were treatment-naive for anti-programmed cell death-1, its ligand, or transforming growth factor β receptor 1 kinase inhibitors. Phase Ib was an open-label, dose-escalation assessment of the safety and tolerability of galunisertib with nivolumab in patients with advanced refractory solid tumors. Phase II evaluated the safety of galunisertib with nivolumab in NSCLC patients who had received prior platinum-based treatment but were immuno-oncology agent-naive. RESULTS: This trial was conducted between October 2015 and August 2020. No dose-limiting toxicities were observed in phase I. In the phase II NSCLC cohort (n = 25), patients received 150 mg twice daily galunisertib (14 days on/14 days off dosing schedule for all phases) plus nivolumab at 3 mg/kg (intravenously every 2 weeks). In this phase, the most frequent treatment-related adverse events (AEs) were pruritus (n = 9, 36%), fatigue (n = 8, 32%), and decreased appetite (n = 7, 28%). No grade 4 or 5 treatment-related AEs were observed. Six (24%) patients had confirmed partial response (PR) and 4 (16%) had stable disease; 1 additional patient had confirmed PR after initial pseudo-progression. The median duration of response was 7.43 months (95% confidence interval [CI]: 3.75, NR). Among the 7 responders, including the delayed responder, 1 had high PD-L1 expression (≥ 50%). The median progression-free survival was 5.26 months (95% CI: 1.77, 9.20) and the median overall survival was 11.99 months (95% CI: 8.15, NR). Interferon gamma response genes were induced post-treatment and cell adhesion genes were repressed, although the association of these observations with tumor response and clinical outcomes was not statistically powered due to limited samples available. CONCLUSIONS: The study met its primary endpoint as galunisertib combined with nivolumab was well tolerated. Preliminary efficacy was observed in a subset of patients in the Phase 2 NSCLC cohort. TRIAL REGISTRATION: Trial registered with ClinicalTrials.gov (NCT02423343; 22.04.2015).

BACKGROUND: Overexpression of Twist1, one of the epithelial-mesenchymal transition-transcription factors (EMT-TFs), is associated with hepatocellular carcinoma (HCC) metastasis. Pelitinib is known to be an irreversible epidermal growth factor receptor tyrosine kinase inhibitor that is used in clinical trials for colorectal and lung cancers, but the role of pelitinib in cancer metastasis has not been studied. This study aimed to investigate the anti-migration and anti-invasion activities of pelitinib in HCC cell lines. METHODS: Using three HCC cell lines (Huh7, Hep3B, and SNU449 cells), the effects of pelitinib on cell cytotoxicity, invasion, and migration were determined by cell viability, wound healing, transwell invasion, and spheroid invasion assays. The activities of MMP-2 and -9 were examined through gelatin zymography. Through immunoblotting analyses, the expression levels of EMT-TFs (Snail1, Twist1, and ZEB1) and EMT-related signaling pathways such as mitogen-activated protein kinases (MAPKs) and Akt signaling pathways were measured. The activity and expression levels of target genes were analyzed by reporter assay, RT-PCR, quantitative RT-PCR, and immunoblotting analysis. Statistical analysis was performed using one-way ANOVA with Dunnett's Multiple comparison tests in Prism 3.0 to assess differences between experimental conditions. RESULTS: In this study, pelitinib treatment significantly inhibited wound closure in various HCC cell lines, including Huh7, Hep3B, and SNU449. Additionally, pelitinib was found to inhibit multicellular cancer spheroid invasion and metalloprotease activities in Huh7 cells. Further investigation revealed that pelitinib treatment inhibited the migration and invasion of Huh7 cells by inducing Twist1 degradation through the inhibition of MAPK and Akt signaling pathways. We also confirmed that the inhibition of cell motility by Twist1 siRNA was similar to that observed in pelitinib-treated group. Furthermore, pelitinib treatment regulated the expression of target genes associated with EMT, as demonstrated by the upregulation of E-cadherin and downregulation of N-cadherin. CONCLUSION: Based on our novel finding of pelitinib from the perspective of EMT, pelitinib has the ability to inhibit EMT activity of HCC cells via inhibition of Twist1, and this may be the potential mechanism of pelitinib on the suppression of migration and invasion of HCC cells. Therefore, pelitinib could be developed as a potential anti-cancer drug for HCC.

Disasters caused by natural phenomena are increasing in frequency and devastation. The growing number of cancer survivors constitute a vulnerable population in their need for continuous and high-level care, a vulnerability that is exacerbated in the event of disasters. Although the evidence base on the needs of cancer survivors is growing, little is known about cancer care in disaster settings. Therefore, we prepared a narrative literature review that outlines existing evidence, identifies knowledge gaps, and clarifies key concepts that are central to the burgeoning area of research into the quality of care for cancer survivors through disasters. As the preponderance of available evidence stresses the importance of careful disaster planning for maintaining care services, this review also provides guidance in developing plans for how to proceed during, and in the aftermath of, disasters.

INTRODUCTION: The overall survival of patients with mesothelioma is poor and heterogeneous. At present, the prediction model for Chinese patients needs to be improved. We sought to investigate predictors of survival in malignant pleural mesothelioma and develop prognostic prediction models. METHODS: This Two-center retrospective cohort study recruited patients with pathologically diagnosed mesothelioma at Beijing Chao-Yang Hospital and Beijing Tong-Ren Hospital. We developed a new prognostic prediction model based on COX multivariable analysis using data from patients who were recruited from June 1, 2010 to July 1, 2021 in Beijing Chao-Yang Hospital (n = 95, development cohort) and validated this model using data from patients recruited from July 18, 2014 to May 9, 2022 in Beijing Tong-Ren Hospital (n = 23, validation cohort). Receiver operating characteristic analysis was used to estimate model accuracy. RESULTS: The parameters in this new model included PLT > 289.5(10^9/L) (1 point), Lymphocyte > 1.785(10^9/L) (-1point), Age > 73 years old (1 point), Calcium > 2.145(mmol/L) (-1point), Eastern Cooperative Oncology Group performance status (ECOG PS) > 2 (2 points). When the sum of scores < 0, it is recognized as a low-risk group; when the score is 0 ~ 3, it is recognized as a high-risk group. The survival rate of patients in the high-risk group was significantly lower than that in the low-risk group (hazard ratio [HR], 3.878; 95% confidence interval [CI], 2.226-6.755; P < 0.001). The validation group had similar results (HR,3.574; 95%CI,1.064-12.001; P = 0.039). Furthermore, the areas under the curve 6 months after diagnosis in the two cohorts were 0.900 (95% CI: 0.839-0.962) and 0.761 (95% CI: 0.568-0.954) for development and validation cohorts, respectively. CONCLUSION: We developed a simple, clinically relevant prognostic prediction model for PLACE by evaluating five variables routinely tested at the time of diagnosis. The predictive model can differentiate patients of Chinese ethnicity into different risk groups and further guide prognosis.

BACKGROUND: To compare the clinical value of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and pegylated rhG-CSF(PEG-rhG-CSF) in early-stage breast cancer (EBC) patients receiving adjuvant chemotherapy, compare the efficacy of PEG-rhG-CSF with different dose and explore the timing of rhG-CSF rescue treatment. METHODS: Patients in two PEG-rhG-CSF subgroups were given 3 mg or 6 mg PEG-rhG-CSF within 24 ~ 48 h after chemotherapy for preventing myelosuppression, while patients in the rhG-CSF group were given rhG-CSF. Observation indicators include the incidence of febrile neutropenia (FN) and grade 3/4 chemotherapy-induced-neutropenia (CIN), the overall levels and nadir values of white blood cells (WBC) and absolute neutrophil count (ANC), comparison of WBC and ANC curves over time, the incidence of CIN-related complications, the incidence of adverse events in each group and the timing of rescue treatment for rhG-CSF. RESULTS: There was no significant difference in the incidence of FN in the first cycle among the groups (P = 0.203). But the incidence of ≥ 3 grade CIN in two PEG-rhG-CSF subgroups was significantly lower than that in the rhG-CSF group (P < 0.001). The overall WBC and ANC levels in the PEG-rhG-CSF group were significantly higher than those in the rhG-CSF group (P < 0.001). In terms of CIN-related complications, less chemotherapy delay rate (1.1 vs. 7.5%, P = 0.092), less dose reduction rate (6.9 vs. 7.5%, P = 1.000), less antibiotic use rate (3.4 vs. 17.5%, P = 0.011) and less proportion of rhG-CSF rescue therapy (24.1 vs. 85.0%, P < 0.001) in the PEG-rhG-CSF group, and there were no significant differences between PEG-rhG-CSF subgroups. In the incidence of adverse events among the groups, there were no statistical differences. All patients undergoing rhG-CSF rescue treatment were mainly 4 grade (63.6%) and 3 grade (25.5%) CIN, and 10.9% of patients with 1 ~ 2 grade CIN who had high infection risk or had been infected. CONCLUSION: PEG-rhG-CSF has better efficacy and equal tolerance compared with rhG-CSF in preventing CIN in EBC patients receiving EC regimen. Moreover, a half-dose 3 mg PEG-rhG-CSF also had good efficacy. Last, patients with ≥ 3 grade CIN and others who have been assessed to be at high risk of infection or have co-infection should consider rhG-CSF or even antibiotic rescue treatment.

BACKGROUND: The COVID-19 pandemic was managed in Aotearoa New Zealand (NZ) by a COVID-19 elimination policy, involving border closure and an initial national lockdown. This was different to most other countries including Northern Ireland (NI) and the Netherlands (NED). We quantify the effect of these policies on the diagnosis of three major cancers, comparing NZ with these two European countries. METHOD: Data from NED, NZ and NI population-based cancer registries were used to assess trends in all pathologically diagnosed (PD) lung, breast, and colorectal cancers from March to December 2020 (pandemic period) and compared to the similar pre-pandemic period (2017-2019). Trend data were also collated on COVID-19 cases and deaths per 100,000 in each population. RESULTS: Comparing the pre-pandemic period to the pandemic period there were statistically significant reductions in numbers of lung (↓23%) and colorectal (↓15%) PD cancers in NI and numbers of breast (↓18%) and colorectal cancer (↓18.5%) diagnosed in the NED. In NZ there was no significant change in the number of lung (↑10%) or breast cancers (↑0.2%) but a statistically significant increase in numbers of colorectal cancer diagnosed (↑5%). CONCLUSION: The impact of COVID-19 on cancer services was mitigated in NZ as services continued as usual reflecting minimal healthcare disruption and protected cancer services linked with the elimination approach adopted. The reduction in PD cases diagnosed in NED and NI were linked with higher COVID-19 rates and reflect societal restrictions which resulted in delayed patient presentation to primary and secondary care, disruption to screening and healthcare services as a result of COVID-19 infections on staff and the need to shift intensive care to COVID-19 patients. Reductions in PD cancers in NI and the NED and in particularly lung cancers in NI, highlight the need for targeted public health campaigns to identify and treat 'missing' patients. Protecting cancer services should be a priority in any future pandemic or systemic healthcare system disruption.

Drug resistance is a major cause of the inefficacy of conventional cancer therapies, and often accompanied by severe side effects. Thus, there is an urgent need to develop novel drugs with low cytotoxicity, high selectivity and minimal acquired chemical resistance. Peptide-based drugs (less than 0.5 kDa) have emerged as a potential approach to address these issues due to their high specificity and potent anticancer activity. In this study, we developed a support vector machine model (SVM) to detect the potential anticancer properties of novel peptides by scanning the American University in Cairo (AUC) Red Sea metagenomics library. We identified a novel 37-mer antimicrobial peptide through SVM pipeline analysis and characterized its anticancer potential through in silico cross-examination. The peptide sequence was further modified to enhance its anticancer activity, analyzed for gene ontology, and subsequently synthesized. To evaluate the anticancer properties of the modified 37-mer peptide, we assessed its effect on the viability and morphology of SNU449, HepG2, SKOV3, and HeLa cells, using an MTT assay. Additionally, we evaluated the migration capabilities of SNU449 and SKOV3 cells using a scratch-wound healing assay. The targeted selectivity of the modified peptide was examined by evaluating its hemolytic activity on human erythrocytes. Treatment with the peptide significantly reduced cell viability and had a critical impact on the morphology of hepatocellular carcinoma (SNU449 and HepG2), and ovarian cancer (SKOV3) cells, with a marginal effect on cervical cancer cell lines (HeLa). The viability of a human fibroblast cell line (1Br-hTERT) was also significantly reduced by peptide treatment, as were the proliferation and migration abilities of SNU449 and SKOV3 cells. The annexin V assay revealed programmed cell death (apoptosis) as one of the potential cellular death pathways in SNU449 cells upon peptide treatment. Finally, the peptide exhibited antimicrobial effects on both gram-positive and gram-negative bacterial strains. The findings presented here suggest the potential of our novel peptide as a potent anticancer and antimicrobial agent.

BACKGROUND: Radiation therapy (XRT) causes numerous biological changes in tumor microenvironment. Radiation vascular response, due to endothelial disruption, can influence treatment outcomes in a dose-dependent manner. Ultrasound-stimulated microbubbles (USMB) have also been demonstrated to create a vascular response in the tumor microenvironment and enhance tumor response when used in combination with XRT. Single doses of 8-10 Gy are known to induce activation of acid sphingomyelinase (ASMase)-induced ceramide production, causing vascular damage. Destruction of vasculature results in endothelial apoptosis followed by tumor cell death. The effect of tumor response is known to be synergistic by 10-fold higher cell kill observed when USMB is combined with radiation. METHODS: In this study, we used an USMB approach in combination with conventional low dose fractionated radiation to enhance endothelial cell responses to XRT in human PC3 prostate cancer xenograft model. Mice were divided into untreated, USMB therapy, fractionated XRT, and combined USMB therapy followed by XRT (USMB + XRT) groups. USMB therapy was delivered twice per week in the USMB-alone and combined USMB + XRT treatment groups over four weeks. Radiation treatments were delivered in fractions of 2 Gy/day (total 40 Gy in 20 fractions, BED10 = 48 Gy) in the XRT-alone and combined USMB + XRT groups. The treatment outcome was evaluated using histopathology, power Doppler, and immunohistochemistry assays. RESULTS: Tumor growth assessment showed that sizes of tumors increased in the control and the single treatment groups over a treatment period of four weeks, but significantly decreased with the combined treatments of USMB + XRT. Immunohistochemical analysis indicated a statistically significant vascular disruption in mice that received treatment involving a full 4-week schedule of combined (USMB + XRT) treatments. A statistically significant increase in vascular disruption was demonstrated through CD68 and trichrome fibrosis staining. Changes in local perfusion assessed using high-frequency power Doppler imaging demonstrated attenuated blood flow in the combined group. DISCUSSION AND CONCLUSIONS: This work demonstrates the efficacy of using USMB as a radiation sensitizer in a mouse model of human PC3 tumor xenograft. This radiation treatment enhancement modality has the advantage of targeting tumor vasculature with ultrasound stimulation that can be implemented prior to radiation treatment.

BACKGROUND: As a component of membrane lipids and the precursor of oxysterols and steroid hormones, reprogrammed cholesterol metabolism contributes to the initiation and progression of multiple cancers. Thus, we aim to further investigate the significances of cholesterol metabolism in lower-grade gliomas (LGGs). METHODS: The present study included 413 LGG samples from TCGA RNA-seq dataset (training cohort) and 172 LGG samples from CGGA RNA-seq dataset (validation cohort). The cholesterol metabolism-related signature was identified by the LASSO regression model. Bioinformatics analyses were performed to explore the functional roles of this signature in LGGs. Kaplan-Meier and Cox regression analyses were enrolled to estimate prognostic value of the risk signature. RESULTS: Our findings suggested that cholesterol metabolism was tightly associated clinicopathologic features and genomic alterations of LGGs. Bioinformatics analyses revealed that cholesterol metabolism played a key role in immunosuppression of LGGs, mainly by promoting macrophages polarization and T cell exhaustion. Kaplan-Meier curve and Cox regression analysis showed that cholesterol metabolism was an independent prognostic indicator for LGG patients. To improve the clinical application value of the risk signature, we also constructed a nomogram model to predict the 1-, 3- and 5-year survival of LGG patients. CONCLUSION: The cholesterol metabolism was powerful prognostic indicator and could serve as a promising target to enhance personalized treatment of LGGs.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with a high prevalence and poor prognosis. It is an urgent problem to deeply understand the molecular mechanism of ESCC and develop effective diagnostic and prognostic methods. METHODS: Using tumor tissue and corresponding paracancerous samples from 141 resected ESCC patients, we assessed Jumonji domain-containing protein 6 (JMJD6) expression using Immunohistochemical (IHC) staining. Kaplan-Meier survival analysis and univariate or multivariate analysis were used to investigate the relationship between JMJD6 expression and clinicopathological features. The expression status and prognostic value of JMJD6 were analyzed by bioinformatics and enrichment analysis. RESULTS: The expression of JMJD6 in ESCC samples was higher than that in the corresponding paracancerous samples, and high expression of JMJD6 was positively associated with poor prognosis of ESCC patients. In addition, bioinformatics analysis of the expression and prognosis of JMJD6 in a variety of tumors showed that high expression of JMJD6 was significantly associated with poor overall survival (OS) in ESCC patients. Enrichment analysis indicated that the high expression of genes similar to JMJD6, such as Conserved oligomeric Golgi 1(COG1), Major facilitator superfamily domain 11 (MFSD11) and Death Effector Domain Containing 2 (DEDD2), was associated with poor prognosis of ESCC, suggesting that JMJD6 might be involved in the occurrence and prognosis of ESCC. CONCLUSION: Our study found that JMJD6 expression was significantly increased in ESCC patients and positively correlated with prognosis, indicating that targeting JMJD6 might be an attractive prognostic biomarker and provides a potential treatment strategy for ESCC. TRIAL REGISTRATION: The study was approved by Tangdu Hospital ethics committee (No. TDLL-202110-02).

BACKGROUND: The Pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) has longer half-life and is given once only, which is more comfortable for patients. We aimed to evaluate the efficacy of mecapegfilgrastim for hematopoietic stem cell (HSC) mobilization in patients with hematologic malignancies and to explore the potential factors related to HSC mobilization. METHODS: A retrospective analysis was performed on patients who underwent HSC mobilization in the hematology department of Mianyang Central Hospital from April 2016 to November 2022. The number of CD34 + cells collected was compared between the patients receiving mecapegfilgrastim (PEG group) and those receiving recombinant human granulocyte colony-stimulating factor (rhG-CSF group), and the possible factors for mobilization failure were analyzed. RESULTS: The success rates of collecting CD34 + cells in the PEG group and rhG-CSF group were 80.6% and 67.7%, respectively (χ = 1.444, P = 0.229). The median CD34 + cell counts were 3.62 × 10^6/kg and 2.92 × 10^6/kg (P = 0.178), respectively. After combination with plerixafor for mobilization, the median number of CD34 + cells collected in the PEG group and rhG-CSF group were 3.64 × 10^6/kg and 3.92 × 10^6/kg, respectively, with no significant difference (P = 0.754). There was no significant difference in hematopoietic cell recovery or infection between the groups (P > 0.05). Multivariate analysis showed that more than 5 cycles of chemotherapy (OR = 15.897, 95% CI: 1.766-143.127, P = 0.014), a precollection WBC count < 32 × 10^9/L (OR = 14.441, 95% CI: 2.180-95.657, P = 0.006) and a precollection to premobilization lymphocyte ratio < 1.7 (OR = 11.388, 95% CI: 2.129-60.915, P = 0.004) were independent risk factors for HSC mobilization failure. CONCLUSIONS: The HSC mobilization efficacy of mecapegfilgrastim in patients with hematologic malignancies was comparable to that of rhG-CSF, and combination with plerixafor for mobilization was feasible and effective. Patients with more than 5 cycles of chemotherapy before HSC mobilization, a precollection WBC count lower than 32 × 10^9/L, and a precollection lymphocyte count less than 1.7 times the premobilization lymphocyte count have a high probability of HSC mobilization failure.

BACKGROUND: The site of lymph node metastasis (LNM) may affect the prognosis of patients with esophageal squamous cell carcinoma (ESCC). To investigate the prognoses of pararespiratory and paradigestive LNM and to propose a novel N (nN) staging system that integrates both the LNM site and count. METHODS: This study was a multicenter, large-sample, retrospective cohort study that included ESCC patients with LNM between January 2014 and December 2019 from three Chinese institutes. Patients were set into training (two institutes) and external validation (one institute) cohorts. The primary outcomes were survival differences in LNM site and the development of novel nodal staging system. The overall survival (OS) of patients with pararespiratory LNM only (Group A), paradigestive LNM only (Group B), and both sites (Group C) was evaluated by Kaplan-Meier. Cox proportional hazards models were used to identify the independent prognostic factors. An nN staging system considering both the LNM site and count was developed and evaluated by the area under the receiver operating characteristic curve (AUC). RESULTS: In total, 1313 patients were included and split into training (n = 1033) and external validation (n = 280) cohorts. There were 342 (26.0%), 568 (43.3%) and 403 (30.7%) patients in groups A, B and C, respectively. The OS of patients with pararespiratory and patients with paradigestive LNM presented significant differences in the training and validation cohorts (P < 0.050). In the training cohort, LNM site was an independent prognostic factor (hazard ratio: 1.58, 95% confidence intervals: 1.41-1.77, P < 0.001). The nN staging definition: nN1 (1-2 positive pararespiratory/paradigestive LNs), nN2 (3-6 pararespiratory LNs or 1 pararespiratory with 1paradigestive LN), nN3 (3-6 LNs with ≥ 1 paradigestive LN), nN4 (≥ 7 LNs). Subsets of patients with different nN stages showed significant differences in OS (P < 0.050). The prognostic model of the nN staging system presented higher performance in the training and validation cohorts at 3-year OS (AUC, 0.725 and 0.751, respectively) and 5-year OS (AUC, 0.740 and 0.793, respectively) than the current N staging systems. CONCLUSIONS: Compared to pararespiratory LNM, the presence of paradigestive LNM is associated with worse OS. The nN staging system revealed superior prognostic ability than current N staging systems.

Our previous work showed that KRAS activation in gastric cancer cells leads to activation of an epithelial-to-mesenchymal transition (EMT) program and generation of cancer stem-like cells (CSCs). Here we analyze how this KRAS activation in gastric CSCs promotes tumor angiogenesis and metastasis. Gastric cancer CSCs were found to secrete pro-angiogenic factors such as vascular endothelial growth factor A (VEGF-A), and inhibition of KRAS markedly reduced secretion of these factors. In a genetically engineered mouse model, gastric tumorigenesis was markedly attenuated when both KRAS and VEGF-A signaling were blocked. In orthotropic implant and experimental metastasis models, silencing of KRAS and VEGF-A using shRNA in gastric CSCs abrogated primary tumor formation, lymph node metastasis, and lung metastasis far greater than individual silencing of KRAS or VEGF-A. Analysis of gastric cancer patient samples using RNA sequencing revealed a clear association between high expression of the gastric CSC marker CD44 and expression of both KRAS and VEGF-A, and high CD44 and VEGF-A expression predicted worse overall survival. In conclusion, KRAS activation in gastric CSCs enhances secretion of pro-angiogenic factors and promotes tumor progression and metastasis.

BACKGROUND: Although 80% of patients with metastatic colorectal cancer (CRC) experience liver metastases, only 10-25% undergo resection at the time of diagnosis. Even in initially unresectable conditions, if appropriate treatment is provided, such as surgical conversion through a combination of hepatic arterial infusion (HAI) chemotherapy and systemic chemotherapy (sys-CT), better overall survival can be expected. Therefore, this study aims to evaluate the efficacy of HAI oxaliplatin in combination with sys-CT plus targeted therapy in patients with unresectable CRC with liver-only metastasis. METHODS: This is a single-center, randomized, open-label phase II trial (NCT05103020). Patients with untreated CRC, who have liver-only metastases and for whom liver resection is potentially possible but deemed infeasible at the time of initial diagnosis by a multidisciplinary team, will be eligible. Patients will be randomly assigned in a 1:1 ratio to either the combined HAI oxaliplatin and modified systemic 5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) plus targeted therapy group or the systemic FOLFIRI plus targeted therapy group. Both regimens will be repeated every 2 weeks for a total of 12 cycles. The primary objective of this study is to compare the rate of conversion to liver resection. The surgical conversion rate is expected to increase by 25% with HAI oxaliplatin in combination with sys-CT plus targeted therapy (40% in the experimental arm versus 15% in the control arm) (power, 80%; two-sided alpha-risk, 5%). The secondary objectives include overall survival, progression-free survival, and objective response rate. DISCUSSION: This is the first randomized controlled trial to investigate the efficacy of HAI oxaliplatin in combination with sys-CT plus targeted therapy as first-line treatment from the initial diagnosis in patients with unresectable CRC with liver-only metastasis, aiming to significantly increase the surgical conversion rate. TRIAL REGISTRATION: ClinicalTrials.gov, (NCT05103020). Trial registration date: November 2, 2021.

BACKGROUND: Numerous studies have demonstrated long noncoding RNA (lncRNA) play an important role in the occurrence and progression of cancer, and single nucleotide polymorphisms (SNPs) located in lncRNA are considered to affect cancer suspensibility. Herein, a meta-analysis was carried out to better assess the relationship of H19 polymorphisms and cancer susceptibility. METHODS: A literature search was conducted through using PubMed, EMBASE, and Web of Science databases to obtain relevant publications before Aug 23, 2022. The reference lists of the retrieved studies were also investigated to identify additional relevant articles. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to appraise the risk of various cancers. RESULTS: There appeared to be a remarkable correlation between the rs2107425 variation and decreased cancer risk among Caucasians. Nevertheless, the rs217727 polymorphism was significantly associated with an increased risk of lung cancer, hepatocellular carcinoma and oral squamous cell carcinoma. Also, we found a significant correlation between the rs2839698 polymorphism and increased cancer risk among Asians, gastric cancer, hepatocellular carcinoma, hospital-based control and larger simple size subgroups, respectively. Similarly, the rs3741219 mutation was notably related to cancer risk in higher quality score. As for rs3024270 polymorphism, the homozygous model was markedly linked to cancer risk in overall analysis and population-based controls. There was no significant association between the rs3741216 polymorphism and cancer risk. CONCLUSION: H19 rs2839698 and rs3024270 were closely associated with overall cancer risk. H19 rs2107425 was related to lower cancer risk among Caucasians, while the rs2839698 was related to increased cancer risk among Asians. Our results supported that H19 SNPs were significantly correlated with cancer risk.

BACKGROUND: Breast cancer (BC) is a significant health concern among European women, with the highest prevalence rates among all cancers. Existing BC prediction models account for major risks such as hereditary, hormonal and reproductive factors, but research suggests that adherence to a healthy lifestyle can reduce the risk of developing BC to some extent. Understanding the influence and predictive role of lifestyle variables in current risk prediction models could help identify actionable, modifiable, targets among high-risk population groups. PURPOSE: To systematically review population-based BC risk prediction models applicable to European populations and identify lifestyle predictors and their corresponding parameter values for a better understanding of their relative contribution to the prediction of incident BC. METHODS: A systematic review was conducted in PubMed, Embase and Web of Science from January 2000 to August 2021. Risk prediction models were included if (i) developed and/or validated in adult cancer-free women in Europe, (ii) based on easily ascertained information, and (iii) reported models' final predictors. To investigate further the comparability of lifestyle predictors across models, estimates were standardised into risk ratios and visualised using forest plots. RESULTS: From a total of 49 studies, 33 models were developed and 22 different existing models, mostly from Gail (22 studies) and Tyrer-Cuzick and co-workers (12 studies) were validated or modified for European populations. Family history of BC was the most frequently included predictor (31 models), while body mass index (BMI) and alcohol consumption (26 and 21 models, respectively) were the lifestyle predictors most often included, followed by smoking and physical activity (7 and 6 models respectively). Overall, for lifestyle predictors, their modest predictive contribution was greater for riskier lifestyle levels, though highly variable model estimates across different models. CONCLUSIONS: Given the increasing BC incidence rates in Europe, risk models utilising readily available risk factors could greatly aid in widening the population coverage of screening efforts, while the addition of lifestyle factors could help improving model performance and serve as intervention targets of prevention programmes.

BACKGROUND: SETD2 protects against genomic instability via maintenance of homologous recombination repair (HRR) and mismatch repair (MMR) in neoplastic cells. However, it remains unclear whether SETD2 dysfunction is a complementary or independent factor to microsatellite instability-high (MSI-H) and tumor mutational burden-high (TMB-H) for immunocheckpoint inhibitor (ICI) treatment, and little is known regarding whether this type of dysfunction acts differently in various types of cancer. METHODS: This cohort study used multidimensional genomic data of 6726 sequencing samples from our cooperative and non-public GenePlus institute from April 1 through April 10, 2020. MSIsensor score, HRD score, RNAseq, mutational data, and corresponding clinical data were obtained from the TCGA and MSKCC cohort for seven solid tumor types. RESULTS: A total of 1021 genes underwent target panel sequencing reveal that SETD2 mutations were associated with a higher TMB. SETD2 deleterious mutation dysfunction affected ICI treatment prognosis independently of TMB-H (p < 0.01) and had a lower death hazard than TMB-H in pancancer patients (0.511 vs 0.757). Significantly higher MSI and lower homologous recombination deficiency were observed in the SETD2 deleterious mutation group. Improved survival rate was found in the MSKCC-IO cohort (P < 0.0001) and was further confirmed in our Chinese cohort. CONCLUSION: We found that SETD2 dysfunction affects ICI treatment prognosis independently of TMB-H and has a lower death hazard than TMB-H in pancancer patients. Therefore, SETD2 has the potential to serve as a candidate biomarker for ICI treatment. Additionally, SETD2 should be considered when dMMR is detected by immunohistochemistry.

PURPOSE: The human EGFR2 (HER2) signaling pathway is one of the most actively studied targets in cancer transformation research. Ttriplex-forming oligonucleotides (TFOs) activate DNA damage and induce apoptosis. We aim to encapsulate TFO-HER2 with nano-particle ZW-128 to suppress breast cell growth in vitro and in vivo. EXPERIMENTAL DESIGN: We designed a set of TFO fragments targeting HER2 and verified their effectiveness. We encapsulated TFO-HER2 in ZW-128 to form nano-drug TFO@ZW-128. Cell counting kit 8, flow cytometry, and western blotting were used to evaluate the effect of TFO@ZW-128 on cell proliferation and the expressions of related proteins. The ant-itumor effect of TFO@ZW-128 was evaluated in vivo using nude mice breast cancer model. RESULTS: TFO@ZW-128 had efficient cellular uptake in amplified HER2 breast cancer cells. TFO@ZW-128 showed an 80-fold increase in TFO utilization compared with TFO-HER2 in the nude mouse breast cancer model. Meanwhile, TFO@ZW-128 dramatically inhibited the growth of HER2-overexpressing tumors compared with TFO-HER2 (P < 0.05). Furthermore, TFO@ZW-128-induced cell apoptosis was in a p53-independent manner. CONCLUSIONS: In this study, we designed nano-drug TFO@ZW-128, which has proven effective and non-toxic in targeted therapy for ectopic HER2-expressing tumors.

BACKGROUND: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in women. Approximately 50% of breast cancers are discovered at an early stage in patients for whom conservative surgery is indicated. Intraoperative localization of non-palpable breast lesions is generally accomplished using a hook wire to mark the area of concern under ultrasound or stereotactic localization. But this technique has several drawbacks (painful, stressful…). We propose the use of a wire-free breast lesion system using miniature radiofrequency identification (RFID) tags. This technique could improve patient comfort and surgical comfort for surgeons. We therefore propose a study to assess the interest of introducing the RFID localization technique at the Jean PERRIN comprehensive cancer center. METHODS: This is a single-center prospective trial designed to assess the interest in introducing the RFID localization technique at the Jean Perrin center. It aims to show the superiority of the RFID technique in terms of patient tolerance compared to the gold-standard (hook wire). A sequential inclusion in time will be performed: 20 inclusions in the gold-standard group, then 20 patients in the RFID group before repeating the inclusion scheme. Any patient requiring preoperative localization will receive a senology consultation. The RFID tag will be placed during this consultation. The hook wire localization will be done the day before the surgery. Patients will fill out a Hospital Anxiety and Depression scale (HAD) questionnaire at the time of inclusion. They will then fill out a satisfaction questionnaire in 2 steps: during the placement of the device (RFID tag or hook wire) or during the postoperative consultation at 1 month. Radiologists and surgeons will fill out a questionnaire to evaluate the localization technique, respectively after the localization and surgery procedures. DISCUSSION: The RFID study is the first study in France which specifically assesses the interest of the RFID localization in terms of patients comfort. Patient comfort is one of the key elements to take into consideration when managing patients in oncology and new technologies such as RFID tags could improve it. TRIAL REGISTRATION: ClinicalTrials.gov ID; NCT04750889 registered on February 11, 2021.

BACKGROUND: RNA binding motif protein 15 (RBM15), a writer of N6-methyladenosine (m6A) methylation, contributes significantly to the development of various tumors. However, the function of RBM15 in cervical cancer (CC) has not been determined. METHODS: Based on the GSE9750, GSE63514, and m6A datasets, m6A-related differentially expressed genes (DEGs) were screened out. The hub genes were identified by generating a Protein-Protein Interaction (PPI) network. RT-qPCR was conducted to assess the mRNA expression of hub genes. CCK8, scratch wound healing, and transwell assays were utilized to examine the influence of RBM15 on HeLa and SiHa cells. Tumor xenograft models were used to assess the effects of RBM15 on tumorigenesis. A mechanistic analysis of RBM15 in CC tumors was conducted using the GeneCards and Coxpresdb databases, followed by a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and the pathway-related genes were subsequently validated using Western blotting. RESULTS: Five DEGs were screened, including WTAP, RBM15, CBLL1, and YTHDC2. Among them, WTAP, RBM15, CBLL1, and YTHDC2 were hub genes and can be used as biomarkers for CC. RBM15 expression was considerably increased, while WTAP, CBLL1, and YTHDC2 were significantly downregulated. Knockdown of RBM15 significantly suppressed the proliferation, invasion, and migration of CC cells and tumorigenesis. Moreover, knockdown of RBM15 significantly reduced the expression levels of proteins related to the JAK-STAT pathway. CONCLUSIONS: Knockdown of RBM15 inhibited the progression of CC cells, which probably by inhibiting the JAK-STAT pathway pathway.

BACKGROUNDS: Tigecycline has a broad spectrum of antimicrobial activity and has been approved for the treatment of complicated intra-abdominal infections. However, it is debatable whether tigecycline should be used alone or in combination. This study aimed to investigate whether tigecycline plus β-lactam antibiotics (combination therapy [CT] group) are superior to tigecycline alone (monotherapy [MT] group) in non-critically ill intra-abdominal infection patients after tumor surgery. METHODS: This was a multicenter, retrospective cohort study. The primary outcome was mortality during the hospital stay. Secondary outcomes were clinical success rate, microbial eradication rate, relapse rate within one week, course of treatment, and adverse effects. Propensity score matching (PSM) was used to adjust the degree of infection before medication between the MT and CT groups. Univariate comparisons were performed using the chi-squared test for qualitative variables and Student's t-test or the Mann-Whitney U-test for continuous variables, as appropriate. Multivariate logistic regression analysis was performed to examine the relationship between antimicrobial treatments and mortality during hospitalization. The paired samples Wilcoxon test was used to compare the parameters before and after medication. RESULTS: In total, 291 patients were included in the final analysis: 128 in MT group and 163 in CT group. Mortality rate was 6.25% in the MT group and 6.13% in the CT group (P = 0.97). Multivariate logistic regression model showed that carbapenem-resistant organisms (OR: 4.35, 95% CI: 2.36 ~ 61.70) and age > 65 (OR: 1.32, 95% CI:1.19 ~ 3.01) were independent risk factors for death. CT group had a shorter defervescence time (P < 0.05), with less likelihood of relapse (P < 0.05) but had a more significant effect on activated partial thromboplastin and prothrombin time. CONCLUSIONS: Tigecycline plus β-lactam wasn't superior to tigecycline monotherapy for the treatment of non-critically ill patients with intra-abdominal infection. But for advanced age patients with cancer, tigecycline combination therapy maybe a better choice in terms of mortality.

BACKGROUND: High risk human papillomaviruses (HR-HPV) have a causal role in cervical oncogenesis, and HIV-mediated immune suppression allows HR-HPV to persist. We studied whether vaginal microbiome community state types (CSTs) are associated with high-grade precancer and/or invasive cervical cancer (HSIL/ICC). METHODS: This was a cross-sectional study of adult women with cervical cancer screening (CCS) at the Jos University Teaching Hospital (JUTH) in Jos, Nigeria, between January 2020 and February 2022. Cervical swabs underwent HPV genotyping (Anyplex™ II HPV28). Cervico-vaginal lavage (CVL) sample was collected for 16 S rRNA gene amplicon sequencing. We used multivariable logistic regression modelling to assess associations between CSTs and other factors associated with HSIL/ICC. RESULTS: We enrolled 155 eligible participants, 151 with microbiome data for this analysis. Women were median age 52 (IQR:43-58), 47.7% HIV positive, and 58.1% with HSIL/ICC. Of the 138 with HPV data, 40.6% were negative for HPV, 10.1% had low-risk HPV, 26.8% had single HR-HPV, and 22.5% had multiple HR-HPV types. The overall prevalence of any HR-HPV type (single and multiple) was 49.3%, with a higher proportion in women with HSIL/ICC (NILM 31.6%, LSIL 46.5%, HSIL 40.8%, and 81.5% ICC; p = 0.007). Women with HIV were more likely to have HSIL/ICC (70.3% vs. 29.7% among women without HIV). In crude and multivariable analysis CST was not associated with cervical pathology (CST-III aOR = 1.13, CST-IV aOR = 1.31). However, in the presence of HR-HPV CST-III (aOR = 6.7) and CST-IV (aOR = 3.6) showed positive association with HSIL/ICC. CONCLUSION: Vaginal microbiome CSTs were not significantly associated with HSIL/ICC. Our findings suggest however, that CST could be helpful in identifying women with HSIL/ICC and particularly those with HR-HPV. Characterization of CSTs using point-of-care molecular testing in women with HR-HPV should be studied as an approach to improve early detection and cervical cancer prevention. Future longitudinal research will improve our understanding of the temporal effect of non-optimal CST, HR-HPV, and other factors in cervical cancer development, prevention, and control.

BACKGROUND: Interindividual survival and recurrence rates in cases of locoregional colon cancer following surgical resection are highly variable. The aim of the present study was to determine whether elevated pre-operative and post-operative CEA values are useful prognostic biomarkers for patients with stage I-III colon cancer who underwent surgery with curative intent. METHODS: We conducted a retrospective study in patients with histologically confirmed stage I-III primary colonic adenocarcinoma who underwent radical surgical resection at Mexico's National Cancer Institute, between January 2008 and January 2020. We determined pre-operative and post-operative CEA and analyzed the association of scores with poorer survival outcomes in patients with resected colon cancer, considering overall survival (OS) and disease-free survival (DFS). RESULTS: We included 640 patients with stage I-III colon cancer. Pre-operative CEA levels were in the normal range in 460 patients (group A) and above the reference value in the other 180. Of the latter, 134 presented normalized CEA levels after surgery, but 46 (group C) continued to show CEA levels above the reference values after surgery. Therefore, propensity score matching (PSM) was carried out to reduce the bias. Patients were adjusted at a 1:1:1 ratio with 46 in each group, to match the number in the smallest group. Median follow- up was 46.4 months (range, 4.9-147.4 months). Median DFS was significantly shorter in Group C: 55.5 months (95% CI 39.6-71.3) than in the other two groups [Group A: 77.1 months (95% CI 72.6-81.6). Group B: 75.7 months (95% CI 66.8-84.5) (p-value < 0.001)]. Overall survival was also significantly worse in group C [57.1 (95% CI 37.8-76.3) months] than in group A [82.8 (95% CI 78.6-86.9 months] and group B [87.1 (95% CI 79.6-94.5 months] (p-value = 0.002). To identify whether change in CEA levels operative and post-surgery was an independent prognostic factor for survival outcomes, a Cox proportional hazard model was applied. In multivariate analysis, change in CEA level was a statistically significant, independent prognostic factor for overall survival (p-value = 0.031). CONCLUSIONS: When assessed collectively, pre-operative and post-operative CEA values are useful biomarkers for predicting survival outcomes in patients with resected colon cancer. Prognoses are worse for patients with elevated pre-operative and post-surgical CEA values, but similar in patients with normal post-surgical values, regardless of their pre-surgery values.

BACKGROUND: A majority of prostate cancer cells are in a non-proliferating, G0 (quiescent) phase of the cell cycle and may lie dormant for years before activation into a proliferative, rapidly progressing, disease phase. Many mechanisms which influence proliferation and quiescence choices remain to be elucidated, including the role of non-coding RNAs. In this study, we investigated the role of a long non-coding RNA (lncRNA), SNHG1, on cell proliferation, quiescence, and sensitivity to docetaxel as a potential factor important in prostate cancer biology. METHODS: Publically available, anonymous, clinical data was obtained from cBioPortal for analysis. RNAi and prostate cancer cell lines were utilized to investigate SNHG1 in vitro. We measured G0 cells, DNA synthesis, and cell cycle distribution by flow cytometry. Western blotting was used to assess G2 arrest and apoptosis. These parameters were also investigated following docetaxel treatment. RESULTS: We discovered that in prostate cancer patients from The Cancer Genome Atlas (TCGA) data set, high SNHG1 expression in localized tumors correlated with reduced progression-free survival, and in a data set of both primary and metastatic tumors, high SNHG1 expression was associated with metastatic tumors. In vitro analysis of prostate cancer cell lines showed SNHG1 expression correlated with a quiescent versus proliferative phenotype. Knockdown of SNHG1 by RNAi in PC3 and C4-2B cells resulted in an accumulation of cells in the G0 phase. After knockdown, 60.0% of PC3 cells were in G0, while control cultures had 13.2% G0. There were reciprocal decreases in G1 phase, but little impact on the proportion of cells in S and G2/M phases, depending on cell line. DNA synthesis and proliferation were largely halted- decreasing by 75% and 81% in C4-2B and PC3 cells, respectively. When cells were treated with docetaxel, SNHG1-depleted C4-2B and PC3 cells were resistant to G2 arrest, and displayed reduced apoptosis, as indicated by reduced cyclin B1 and cleaved caspase 3, suggesting SNHG1 levels may modulate drug response. CONCLUSIONS: Overall, these results indicate SNHG1 has complex roles in prostate cancer, as it stimulates cell cycle entry and disease progression, but sensitizes cells to docetaxel treatment.

BACKGROUND: Current guidelines only propose the importance of perineural invasion(PNI) on prognosis in stage II colon cancer. However, the prognostic value of PNI in other stages of colorectal cancer (CRC) is ambiguous. METHODS: This single-center retrospective cohort study included 3485 CRC patients who underwent primary colorectal resection between January 2013 and December 2016 at the Sixth Affiliated Hospital of Sun Yat-sen University. Associations of PNI with overall survival (OS) and disease-free survival (DFS) were evaluated using multivariable Cox proportional hazards regression models. In addition, interaction analyses were performed to explore the prognostic effects of PNI in different clinical subgroups. RESULTS: After median follow-up of 61.9 months, we found PNI was associated with poorer OS (adjusted hazard ratio [aHR], 1.290; 95% CI, 1.087-1.531) and DFS (aHR, 1.397; 95% CI, 1.207-1.617), irrespective of tumor stage. Interestingly, the weight of PNI was found second only to incomplete resection in the nomogram for risk factors of OS and DFS in stage II CRC patients. Moreover, OS and DFS were insignificantly different between stage II patients with PNI and stage III patients (both P > 0.05). PNI was found to be an independent prognostic factor of DFS in stage III CRC (aHR: 1.514; 95% CI, 1.211-1.892) as well. Finally, the adverse effect of PNI on OS was more significant in female, early-onset, and diabetes-negative patients than in their counterparts (interaction P = 0.0213, 0.0280, and 0.0186, respectively). CONCLUSION: PNI was an important prognostic factor in CRC, more than in stage II. The survival of patients with stage II combined with perineural invasion is similar with those with stage III. PNI in stage III CRC also suggests a worse survival.

The accumulation of lipid droplets (LDs) in hepatocytes is the main pathogenesis in nonalcoholic fatty liver disease (NAFLD), which is also the key risk factor for the progression of hepatocellular carcinoma (HCC). LDs behaviors are demonstrated to be associated with HCC advancement, and are tightly regulated by a subset protein localized on the surface of LDs. However, the role of LDs-localized protein in HCC has been rarely investigated. This study is focused on the transcriptional dynamic and prognostic value of LDs-localized protein in HCC. Firstly, we summarized the known LDs-localized proteins, which are demonstrated by immunofluorescence according to previous studies. Next, by the use of GEPIA/UALCAN/The Human Protein Atlas databases, we screened the transcriptional change in tumor and normal liver tissues, and found that 13 LDs-localized proteins may involve in the progression of HCC. Then we verified the transcriptional changes of 13 LDs-localized proteins by the use of HCC samples. Moreover, based on the assays of fatty liver of mice and human NAFLD liver samples, we found that the hepatic steatosis mainly contributed to the transcriptional change of selected LDs-localized proteins, indicating the involvement of these LDs-localized proteins in the negative role of NAFLD in HCC progression. Finally, we focused on the role of PLIN3 in HCC, and revealed that NAFLD status significantly promoted PLIN3 transcription in HCC tissue. Functional studies revealed that PLIN3 knockdown significantly limited the migration and chemosensitivity of hepatoma cells, suggesting the positive role of PLIN3 in HCC progression. Our study not only revealed the transcriptional change and prognostic value of lipid droplet-localized proteins in HCC, but also built the correlation between HCC and hepatic steatosis.

PURPOSE: Analyzing the prognostic value of Epstein-Barr virus (EBV) DNA load and platelet-to-lymphocyte ratio (PLR) in non-metastatic nasopharyngeal carcinoma (NPC) patients, thereby developing a reliable and effective marker. METHODS: We compared survival rates among different groups using the Kaplan-Meier method and the Log-rank test. The factors affecting the prognosis of NPC patients were determined using univariate and multivariate cox regression analysis. Receiver operating characteristic (ROC) curves were used to identify the cutoff-value and discriminant performance of the model. RESULTS: The ROC curve indicated a cut-off value of 775 copies/ml for EBV DNA and 203.3 for PLR. Kaplan-Meier and Log-rank tests showed that 3-year overall survival (OS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) of NPC patients in high risk group (HRG) were significantly poorer than those in medium risk group (MRG) and low risk group (LRG). The 3-year OS of NPC patients was significantly correlated with age, N stage and EBV DNA-PLR. The 3-year LRFS were significantly correlated with sex, N stage, histology type, and EBV DNA-PLR. The 3-year DMFS were correlated with histology type. The ROC curve showed that area under the curve (AUC) values of EBV DNA-PLR of 3-year OS, LRFS and DMFS in NPC were higher than those of PLR and EBV DNA. CONCLUSION: EBV DNA-PLR is an independent risk factor for the prognosis of NPC. Compared with PLR or EBV DNA alone, the combination of EBV DNA and PLR may be more accurate in predicting the prognosis of NPC patients.

BACKGROUND: Rat sarcoma viral oncogene homolog (RAS) gene mutation is a common molecular event in colorectal cancer (CRC). The prognosis of mCRC (metastatic colorectal cancer) patients with RAS mutation is poor and capecitabine and oxaliplatin (CapeOx) plus bevacizumab has shown to be one of the standard therapeutic regimens as first line for these patients with objective response rate (ORR) of ~ 50% and median progression-free survival (mPFS) of 8-9 months. Immunotherapy, especially anti-programmed death 1 (PD-1) monoclonal antibody has demonstrated ground-breaking results in deficient mismatch repair (dMMR) / microsatellite instability-high (MSI-H) mCRC patients. However, the response rate of in microsatellite stable (MSS) patients is extremely low. In addition, preclinical studies have demonstrated that anti-Vascular endothelial growth factor (VEGF) agents, such as bevacizumab, can induce tumor vascular normalization and enhance antitumor immunity. Previous study indicated the combination of chemotherapy, anti-VEGF agents (bevacizumab) with immune checkpoint inhibitors may have promising clinical activity in RAS mutant, MSS refractory mCRC patients. Based on these evidences, we will explore the combination of CapeOx with bevacizumab and sintilimab (anti-PD-1 monoclonal antibody) in RAS mutant, MSS mCRC patients as first-line therapy. METHODS: This is a randomized, open-label, multicentric clinical trial. In the sintilimab arm, patients will receive sintilimab in combination with CapeOx and bevacizumab. In the control arm, patients will receive CapeOx and bevacizumab. This trial will recruit 494 patients from 20 centers and randomly (1:1) disseminated into two groups. The primary endpoint is the PFS. The secondary endpoints include overall survival, safety, ORR, and disease control rate. DISCUSSION: This study may provide new ideas for optimizing oncology treatment planning for RAS mutant, MSS mCRC patients in the first-line set. TRIAL REGISTRATION: This study is short for BBCAPX and has been registered at clinicaltrials.gov registry with identifier NCT05171660.

BACKGROUND: Annexins are a family of proteins involved in a wide variety of cellular processes such as inflammation, proliferation, differentiation, apoptosis, migration and membrane repair. However, the role of most Annexins in renal cell carcinoma (RCC) remained unclear. METHODS: The differentially expressed Annexins in RCC compared with normal controls were screened applying the TCGA database. The correlation of differentially expressed Annexins with clinical stages, grades and overall survival was analyzed to explore the clinical significance of Annexins in RCC. Then ANXA8 was selected and further stained in the discover and validation RCC cohort. The correlation of ANXA8 expression with clinical parameter was verified at the protein level. To explore the potential function of ANXA8, ANXA8 was knockdown in the RCC cell line and further analyzed using transcriptome and bioinformatic analysis. RESULTS: mRNA expression of ANXA1, ANXA2R, ANXA4, ANXA8, ANXA8L1 and ANXA13 were significantly upregulated in RCC compared with normal kidney tissues. In contrast, ANXA3 and ANXA9 mRNA expression was significantly downregulated. Higher expression of ANXA2R, ANXA8 and ANXA8L1 were correlated with worse overall survival, while lower expression of ANXA3, ANXA9 and ANXA13 were associated with worse clinical outcomes in RCC patients. We further demonstrated that ANXA8 expression was significantly increased in RCC compared with normal renal tissues at the protein level. And higher protein expression of ANXA8 was associated with higher clinical grades. Through the bioinformatics analysis and cell cycle analysis, we found knockdown of ANXA8 mainly influenced the cell cycle and DNA replication. The top ten hub genes consist of CDC6, CDK2, CHEK1, CCNB1, ORC1, CHEK2, MCM7, CDK1, PCNA and MCM3. CONCLUSIONS: Multiple members of Annexins were abnormally expressed and associated with the prognosis of RCC. The expression of ANXA8 was significantly increased in RCC and associated with poor prognosis. ANXA8 might influence the cell cycle and could be a potential biomarker and therapeutic target for RCC.

BACKGROUND: Previous studies have shown that Family with sequence similarity 134 member B (FAM134B) was involved in the occurrence and development of malignancy, however, the function and molecular mechanism of FAM134B in Hepatocellular Carcinoma (HCC) radiotherapy resistance remain unclear. Therefore, it may clinical effective to clarify the molecular mechanism and identify novel biomarker to overcome radiotherapy resistance in HCC. METHODS: The protein and mRNA expression of FAM134B were determined using Real-time PCR and Western blot, respectively. IHC assay was performed to investigate the association between FAM134B expression and the clinicopathological characteristics of 132 HCC patients. Functional assays, such as in situ model, colon formation, FACS, and Tunel assay were used to determine the oncogenic role of FAM134B in human HCC progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of FAM134B promotes radiation-sensitive in HCC cells. RESULTS: We noted that FAM134B was downregulated in HCC, which was correlated with the radiation resistance in patients with HCC. Overexpression of FAM134B contribute to radiation sensitive in HCC; however, inhibition of FAM134B confers HCC cell lines to radiation resistance both in vitro and in vivo. Moreover, we found that FAM134B interacts with FMS related receptor tyrosine kinase 3 (FLT3) and downregulation of FAM134B activated JAK/Stat3 signaling pathway. Importantly, pharmacological inhibition of JAK/Stat3 signaling pathway significantly counteracted downregulation of FAM134B-induced radiation resistance and enhanced radiation therapeutic efficacy in HCC. CONCLUSIONS: Our findings suggest that FAM134B may be a potential therapeutic biomarker for the treatment of HCC patients with radiotherapy tolerance.

BACKGROUND: Neuroblastoma (NB) is a childhood malignant tumor,50% of high-risk NB children still have recurrence, and the long-term survival rate is very low. NB tumors expressing high levels of BDNF/TrkB are associated with poor survival outcomes.In this study, we show that the trends of serum concentration of BDNF at different growth stages after birth, and explore the relationship with NB replase. METHODS: In experiment 1, 87 subjects were enrolled and divided into four groups, neonates group、 children group、adults group and NB patients. The distribution of serum concentration of BDNF by ELISA. In experiment 2, we studied BDNF in stage 4 NB patients to determine their frequency, correlation with clinical parameters, and prognostic impact. RESULTS: First, we identified that serum BDNF concentration decreased from the newborn to childhood in healthy subjects, while it was relatively high in children(age > 1 year) with NB. In the second phase our studies showed no significant increase in serum BDNF concentration in these NB patients, with adverse pathologic features, large tumor maximum diameter, and MYCN amplification. After comprehensive treatment, levels of BDNF gradually increased in children with recurrence and decreased in the remission group. High serum BDNF concentration was associated with relapse. Of 21 stage 4 neuroblastoma patients, adopted a comprehensive treatment approach including ATO-basic modified chemotherapy, traditional radiotherapy,stem cell transplatation and immunotherapy. 76% of alive patients having > 3 years follow-up. CONCLUSION: The aim is to show that BDNF is a predictor of recurrence risk of NB.

BACKGROUND: Patients diagnosed with esophageal cancer demonstrate a low overall survival even despite the established multimodal therapy as the current standard of care. Therefore, further biomarkers for patients with high-risk and additional therapy options are needed. NANOG is a transcription factor, which can be found in stem cells and is known to support tumorigenesis. METHODS: Six hundred sixty patients with esophageal adenocarcinoma, who were operated at the University of Cologne with a curative intent, were included. Immunohistochemical stainings for NANOG were performed. The study population was divided into NANOG-positive and -negative subgroups. RESULTS: Positive NANOG expression correlates significantly with worse overall survival (p = 0.002) and could be confirmed as an independent risk factor for worse patient survival in multivariate analysis (HR = 1.40, 95%CI = 1.09-1.80, p = 0.006). This effect could be detected in the subgroup of primarily operated patients, but not in patients after neoadjuvant therapy. CONCLUSIONS: We describe a NANOG-positive subgroup of patients with esophageal cancer, who exhibit worse overall survival in a large patient cohort. This discovery suggests the potential use of NANOG as a biomarker for both intensified therapy and stricter follow-up regimes. Additionally, NANOG-positive stem cell-like cancer cells could be used as a new antitumoral treatment target if validated in mechanistic and clinical studies.

BACKGROUND: Studies have shown that microRNA-191 (miR-191) is involved in the development and progression of a variety of tumors. However, the function and mechanism of miR-191 in oral squamous cell carcinoma (OSCC) have not been clarified. METHODS: The expression level of miR-191 in tumor tissues of patients with primary OSCC and OSCC cell lines were detected using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. OSCC cells were treated with miR-191 enhancers and inhibitors to investigate the effects of elevated or decreased miR-191 expression on OSCC cells proliferation, migration, cell cycle, and tumorigenesis. The target gene of miR-191 in OSCC cells were analyzed by dual-Luciferase assay, and the downstream signaling pathway of the target genes was detected using western blot assay. RESULTS: The expression of miR-191 was significantly upregulated in OSCC tissues and cell lines. Upregulation of miR-191 promoted proliferation, migration, invasion, and cell cycle progression of OSCC cells, as well as tumor growth in nude mice. Meanwhile, reduced expression of miR-191 inhibited these processes. Phospholipase C delta1 (PLCD1) expression was significantly downregulated, and negatively correlated with the expression of miR-191 in OSCC tissues. Dual-Luciferase assays showed that miR-191-5p could bind to PLCD1 mRNA and regulate PLCD1 protein expression. Western blot assay showed that the miR-191 regulated the expression of β-catenin and its downstream gene through targeting PLCD1. CONCLUSION: MicroRNA-191 regulates oral squamous cell carcinoma cells growth by targeting PLCD1 via the Wnt/β-catenin signaling pathway. Thus, miR-191 may serve as a potential target for the treatment of OSCC.

BACKGROUND: Seroma is the most common complication following breast cancer surgery, with reported incidence up to 90%. Seroma causes patient discomfort, is associated with surgical site infections (SSI), often requires treatment and increases healthcare consumption. The quilting suture technique, in which the skin flaps are sutured to the pectoralis muscle, leads to a significant reduction of seroma with a decrease in the number of aspirations and surgical site infections. However, implementation is lagging due to unknown side effects, increase in operation time and cost effectiveness. Main objective of this study is to assess the impact of large scale implementation of the quilting suture technique in patients undergoing mastectomy and/or axillary lymph node dissection (ALND). METHODS: The QUILT study is a stepped wedge design study performed among nine teaching hospitals in the Netherlands. The study consists of nine steps, with each step one hospital will implement the quilting suture technique. Allocation of the order of implementation will be randomization-based. Primary outcome is 'textbook outcome', i.e.no wound complications, no re-admission, re-operation or unscheduled visit to the outpatient clinic and no increased use of postoperative analgesics. A total of 113 patients is required based on a sample size calculation. Secondary outcomes are shoulder function, cosmetic outcome, satisfaction with thoracic wall and health care consumption. Follow-up lasts for 6 months. DISCUSSION: This will be one of the first multicentre prospective studies in which quilting without postoperative wound drain is compared with conventional wound closure. We hypothesize that quilting is a simple technique to increase textbook outcome, enhance patient comfort and reduce health care consumption.

BACKGROUND: Recurrences are the main reasons for unfavorable outcomes for patients with stage II colorectal cancer (CRC). To obtain a clear understanding of the high-risk factors, further investigation is warranted. The present study aimed to analyze the risk factors associated with postoperative recurrence in patients with stage II CRC. METHODS: Eligible patients with pathologically confirmed stage II CRC were enrolled in the study retrospectively based on a prospectively maintained database from April 2008 to March 2019. The Kaplan-Meier method were used to calculate the overall survival (OS) rate and the cumulative recurrence rate. Univariate and multivariable Cox regression analyses were performed to identify risk factors for recurrence. RESULTS: There were 2515 patients included, of whom 233 (9.3%) developed local or distant recurrence. Recurrence was associated with a significantly worse 5-year OS (45.4% vs. 95.5%, p < 0.0001). The 5-year cumulative recurrence rate was 13.0% in patients with stage II CRC. On multivariable Cox analysis, tumor size (Hazard Ratio (HR) [95% confidence interval (CI)] = 1.79[1.38, 2.33]), preoperative carbohydrate antigen (CA) 125 level (HR [95% CI] = 1.78[1.17, 2.70]), preoperative CA 199 level (HR [95% CI] = 1.56[1.09, 2.22]), and ulcerating tumor (HR [95% CI] = 1.61[1.19, 2.17]) were found to be associated with postoperative recurrence. Adjuvant chemotherapy was associated with a lower cumulative recurrence rate in patients with these risk factors (p = 0.00096). CONCLUSION: The tumor diameter, preoperative CA125 level, preoperative CA199 level, and an ulcerative tumor can predict postoperative recurrence in patients with stage II CRC, and postoperative chemotherapy could reduce the cumulative recurrence rate in patients with these high-risk factors.

BACKGROUND: V domain Immunoglobulin suppressor of T cell activation (VISTA) has been proved to be a novel immune checkpoint molecule that positively regulates T cell infiltration in several malignancies. However, the clinical impact of VISTA on muscle-invasive bladder cancer (MIBC) patients remains relatively obscure. METHODS: This study enrolled 135 MIBC patients from Zhongshan Hospital (ZSHS) and 391 patients from The Cancer Genome Atlas (TCGA) to examine the VISTA expression and immune contexture based on immunohistochemistry (IHC) staining and CIBERSORT algorithm. Additionally, IMvigor210 Cohort included 195 bladder-derived urothelial carcinoma patients to evaluate the efficacy of immunotherapy. Kaplan-Meier curve and Cox regression analyses were conducted to assess clinical outcomes. RESULTS: MIBC patients with high VISTA+ immune cells (ICs) possessed poor overall survival and inferior therapeutic responsiveness to adjuvant chemotherapy (ACT), but superior responsiveness to PD-L1 inhibitor. VISTA+ ICs infiltration shaped an immunoevasive context featured by regulatory T cells (Tregs), M2 macrophages, mast cells and exhausted CD8+ T cells infiltration, with increased interleukin 10 (IL-10), transforming growth factor-β (TGF-β) and interferon-γ (IFN-γ), but also elevated T-cell immunoglobulin mucin-3 (TIM-3), lymphocyte activation gene 3 (LAG-3) and T-cell immunoglobulin and ITIM domain (TIGIT), which was also mainly presented in basal-squamous and luminal-infiltrated subtypes of MIBC. CONCLUSION: VISTA+ ICs infiltration could be an independent predictor to identify poor prognosis and therapeutic responses (PD-L1 blockade and ACT) in MIBC patients, which was associated with immunoevasive contexture. The novel immune checkpoint VISTA might be utilized as a candidate treatment biomarker in MIBC patients.

BACKGROUND: Clinical studies have shown that first-line use of anti-angiogenetic therapy can prolong progression-free survival but little progress has been made in extending the overall survival of the patients. We explored the role of ELK3 in glioma angiogenesis to improve and design more efficacious therapies. METHODS: A tissue microarray and immunohistochemistry analysis were used to determine the expression of ELK3 protein in 400 glioma patients. Cell proliferation, metastasis, cell cycle, and apoptosis were monitored in U87 and U251 cells using CCK-8, EdU, transwell assays, and flow cytometry. A tube-formation assay, a rat aorta ring sprouting assay, and a matrigel plug assay were performed to examine the antiangiogenic activity of ELK3. An ELISA, Western blot, and correlation analysis of the CGGA dataset were used to detect the association between ELK3 and VEGF-A or ELK3 and HIF-1[Formula: see text]. Besides, orthotopic transplantation in nude mice and histopathological and immunological analysis of in vitro tumors were used to explore the effect of ELK3 on tumor progression and median survival. RESULTS: ELK3 was upregulated in glioma tissues and associated with a poor prognosis. In vitro, ELK3 promoted cell proliferation and cell cycle progression, induced metastasis, and suppressed apoptosis. Then, silencing ELK3 inhibited VEGF-A expression and secretion by facilitating HIF-1[Formula: see text] degradation via ubiquitination. Finally, knockdown ELK3 inhibited tumor progression and angiogenesis in vitro and in vivo, as well as prolonged nude mice's median survival. CONCLUSIONS: Our findings first evidenced that ELK3 is crucial for glioma because it promotes angiogenesis by activating the HIF-1[Formula: see text]/VEGF-A signaling axis. Therefore, we suggest that ELK3 is a prognostic marker with a great potential for glioma angiogenesis and ELK3-targeted therapeutic strategies might hold promise in improving the efficacy of anti-angiogenic therapies.

BACKGROUND AND AIM: Necroptosis plays an important role in hepatocellular carcinoma (HCC) development, recurrence, and immunotherapy tolerance. We aimed to build a new prognostic necroptosis-related gene signature that could be used for survival and immunotherapy prediction in HCC patients. METHODS: We found that necroptosis was associated with HCC progression and survival outcomes and was involved in the immune infiltration of HCC. Multiple bioinformatics methods including WGCNA, LASSO-Cox regression, stepwise Cox regression, and Random Forest and Boruta model analysis, were used to establish a prognostic profile related to necroptosis. The necroptosis-related gene signature was validated in ICGC and GSE14520 datasets. RESULTS: This five-gene signature showed excellent predictive performance and was an independent risk factor for patients' overall survival outcome in the three cohorts. Moreover, this signature was an exact predictor using fewer genes than previous gene signatures. Finally, qRT-PCR and immunohistochemical staining investigations were performed in previously collected fresh frozen tumor tissues from HCC patients and their paracancerous normal tissues, and the results were consistent with the bioinformatics results. We found that LGALS3 not only affected the proliferation and migration ability of HepG2 cells but also affected necroptosis and the expression of inflammatory cytokines. CONCLUSION: In summary, we established and validated an individualized prognostic profile related to necroptosis to forecast the therapeutic response to immune therapy, which might offer a potential non-apoptotic therapeutic target for HCC patients.

BACKGROUND: Although there is extensive literature on correlates of health-related quality of life (HRQoL) among cancer survivors, there has been less attention paid to the role of socioeconomic disadvantage and survivorship care transition experiences in HRQoL. There are few large cohort studies that include a comprehensive set of correlates to obtain a full picture of what is associated with survivors' HRQ0L. This cohort study of recent cancer survivors in New Jersey aimed to explore the association between social determinants of health, health history, health behaviors, survivorship care experiences, and psychosocial factors in HRQoL. METHODS: Eligible survivors were residents of New Jersey diagnosed with genitourinary, female breast, gynecologic, colorectal, lung, melanoma, or thyroid cancers. Participants completed measures of social determinants, health behaviors, survivorship care experiences, psychosocial factors, and HRQoL. Separate multiple regression models predicting HRQoL were conducted for each of the five domains (social determinants, health history, health behaviors, survivorship care experiences, psychosocial factors). Variables attaining statistical significance were included in a hierarchical multiple regression arranged by the five domains. RESULTS: 864 cancer survivors completed the survey. Lower global HRQoL was associated with being unemployed, more comorbidities, a less healthy diet, lower preparedness for survivorship, more unmet support needs, and higher fear about cancer recurrence. Two psychosocial factors, unmet support needs and fear of recurrence, played the most important role in HRQoL, accounting for more than 20% of the variance. Both unmet support needs and fear of recurrence were significant correlates of physical, functional, and emotional HRQoL domains. CONCLUSIONS: Interventions seeking to improve cancer survivors' HRQoL may benefit from improving coordinated management of comorbid medical problems, fostering a healthier diet, addressing unmet support needs, and reducing survivors' fears about cancer recurrence.

BACKGROUND: Cancer risk varies geographically, and migrants are influenced by different risk factors before, during and after migration. Increased migration from non-Western countries to the Nordic countries calls for a better understanding of the migrants' cancer risk and the change in risk patterns over time. The aim of this study was to compare the incidence and mortality of breast, colorectal and lung cancer between non-Western immigrant and the native female population in Denmark, Finland, Iceland, and Norway. MATERIAL AND METHODS: Data from national registries were processed and pre-analysed in each country. Multivariate Poisson regression models were used to model the relative differences in incidence and mortality as rate ratios (RR). The country-specific estimates and summary statistics were pooled together using a random effects model. RESULTS: Non-Western immigrant women had significantly lower breast (RR 0.71, 0.65-0.78), colorectal (RR 0.72, 0.57-0.92) and lung (RR 0.55, 0.42-0.72) cancer incidence rates than native women, and the risk of these cancers among immigrant women increased with duration of residence. Differences were parallel in breast, colorectal and lung cancer mortality (RR 0.64, 0.55-0.74; RR 0.66, 0.48-0.92; RR 0.51, 0.34-0.79). Among immigrant women, higher education increased the risk for breast cancer and decreased it for lung cancer. CONCLUSION: The results significantly complement and add to the previous findings of cancer burden and cancer burden transition among migrants and provide evidence of a prolonged cancer risk advantage among non-Western immigrant women. However, the findings show an increasing risk of lifestyle-related cancers with increasing duration of residence in the host country. Further studies are needed to discover underlying reasons for this phenomenon.

BACKGROUND: Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC) have a poor prognosis and limited therapeutic options. Immune checkpoint inhibitors (ICIs) are effective in patients with tumor progression < 6 months following first-line, platinum-based chemotherapy (PBC), but data are missing for patients with progression ≥ 6 months after the last platinum dose. METHODS: Retrospective analysis (six French centers, 2008-2019) of all consecutive R/M-HNSCC patients. treated first-line with PBC and tumor progression ≥ 6 months after the last platinum dose. PRIMARY ENDPOINT: progression-free survival after second-line therapy (PFS2). Additional endpoints: overall survival from Day 1 of first-line (OS1) and second-line (OS2) therapy. RESULTS: R/M-HNSCC patients (n = 144) received cisplatinum (n = 67, 47%) or carboplatinum (n = 77, 53%) first-line. Response after first-line: complete response (CR; n = 16, 11%); partial response (PR; n = 77, 53%); stable disease (n = 22, 15%). Second-line therapy: PBC (n = 95, 66%); platinum-free regimen (PFR) (n = 25, 17%); ICI (n = 24, 17%). Median [95% confidence interval] PFS (months): PBC 5.0 [3.8-6.2]; PFR 4.0 [1-7.0]; ICI 2.0 [0.4-3.6] (p = 0.16). For PBC, PFR, and ICI, respectively: OS1 30, 23, and 29 months (p = 1.02); OS2 14, 10, and 16 months (p = 0.25); PR, 26%, 16%, and 21% patients; CR, 0%, 8%, and 4% patients. For subsequent lines, ICIs were administered for PBC (n = 11, 12%) and PFR (n = 2, 8%). No predictive factor for efficacy (PFS, OS) was identified. CONCLUSIONS: Our retrospective study suggests similar efficacy regarding OS2 for second-line chemotherapy or ICI in R/M-HNSCC patients with progression ≥ 6 months after the last first-line platinum dose.

BACKGROUND: In non-small cell lung cancer (NSCLC), there may be a relationship between programmed death-ligand 1 (PD-L1) expression, driver mutations and cigarette smoking. METHODS: In this single-center retrospective study, the relationship between common driver mutations (EGFR mutation and ALK rearrangement) and PD-L1 expression in advanced NSCLC according to the patients' smoking history was examined. Light, moderate and heavy smokers had smoked < 20, 20-39, and ≥ 40 pack-years, respectively. The level of PD-L1 expression, assessed using Ventana SP263 monoclonal antibody assay, was defined by the tumor proportion score (TPS) as high expression (TPS ≥ 50%), low expression (TPS 1%-49%) and no expression (TPS < 1%). RESULTS: 101 (52.9%) of 191 advanced NSCLC patients were never smokers. EGFR mutations were more common in never smokers (64.4%) than in smokers (17.8%) with advanced NSCLC (P < 0.0001). A higher proportion of smokers (26.7%) had high PD-L1 expression compared to never smokers (13.9%) (P = 0.042). There was a trend for a higher proportion of male NSCLC patients [28 of 115 (24.3%)] than female patients [10 of 76 (13.2%)] to have high PD-L1 expression (P = 0.087]. High PD-L1 expression was seen in 32 of 110 (29.1%) patients with EGFR wild-type NSCLC but only in 6 of 81 (7.4%) patients with EGFR-mutant tumors (P < 0.0001). Among the 90 smokers with NSCLC, a higher proportion of heavy smokers (35.8%) than non-heavy smokers (13.5%) had high PD-L1 expression (P = 0.034). In patients with adenocarcinoma, high PD-L1 expression was seen in 25 of 77 (32.5%) patients with EGFR wild-type tumors but only in 4 of 70 (5.7%) patients with EGFR-mutant tumors (P < 0.0001). Among patients with adenocarcinoma, a significantly higher proportion of ever smokers (29.3%) than never smokers (13.5%) had high PD-L1 expression (P = 0.032). Among smokers with adenocarcinoma, a significantly higher proportion of heavy smokers (44.1%) than non-heavy smokers (8.3%) had high PD-L1 expression (P = 0.004). On multivariate analysis, after adjusting for gender and smoking status, heavy smoking and EGFR wild-type tumors remained significantly associated with high PD-L1 expression in NSCLCs and also in adenocarcinoma. CONCLUSIONS: Heavy smoking and EGFR wild-type tumors were significantly associated with high PD-L1 expression in NSCLCs and also in adenocarcinoma.

BACKGROUND: Breast cancer (BC) with low human epidermal growth factor receptor 2 (HER2) expression is attracting much attention due to the breakthrough progress of novel anti-HER2 antibody-drug conjugates. HER2 expression is examined in patients with HER2-low BC and their distant metastases in this study, so as to further clarify the dynamic characteristics of HER2 low status in the process of disease progression. METHODS: Patients diagnosed with HER2 low breast cancer (defined as IHC1+ or IHC2+/ISH-) between 2012 and 2021 were included in this study. We evaluated HER2 expression of primary sites and metastatic sites, compared the impact of different clinicopathological parameters on HER2 status of metastases and compared the overall survival and disease-free survival of patients with different HER2 status in metastases. RESULTS: Ninety-eight patients were included. All HER2 IHC scores were confirmed and the consistent rate with the original pathological report was 81.1%. 27.6% of the patients showed different HER2 status in metastases. The HER2 discordance rate differed among different metastatic sites (p = 0.040). The higher the T stage of the primary BC, the higher the rate of HER2 discordance was observed (p = 0.042). For the specimen type of metastasis, HER2 discordant rate was higher in surgical specimen than biopsy (p = 0.050). No difference of HER2 discordance rate was found between HER2-1+ and HER2-2+ patients. But comparing HER2 IHC score, HER2-2+ patients were less likely to have consistent metastatic HER2 levels than HER2-1+ patients (p = 0.006). No difference in survival outcomes was observed between patients with different HER2 status in metastases. CONCLUSIONS: There is a possibility of HER2 expression alteration in the metastases of HER2-low breast cancer. And the rate of altered HER2 low expression was different among different metastatic sites, different T stages of primary BC and specimen type of metastasis. No prognostic significance was observed.

BACKGROUND: Cancer cells release heterogeneous populations of extracellular vesicles (EVs) that transmit aggressive phenotypic traits to recipient cells. We aimed to establish if the heterogenous EVs population or a sub-population is responsible, if we could block undesirable cell-to-cell communication by EVs, and, if some EVs continued to be released, would their undesirable influences on recipient cells continue. METHODS: Three triple-negative breast cancer (TNBC) cell lines were used. Non-toxic concentrations of calpeptin, Y27632, manumycin A, GW4869 and combinations thereof were tested to block EVs. Ultracentrifugation-based methods collected EVs, which were then characterised by nanoparticle tracking analysis, immunoblotting, and transmission electron microscopy. A quick screening flow cytometry method evaluated EVs in solution. The influences of EVs on recipient cells' migration was investigated. RESULTS: All EV sub-populations were apparently involved in transmitting undesirable phenotypic characteristics. All compounds/combinations significantly (64-98%) reduced EVs' release. Our quick screening broadly reflected our more comprehensive EVs analysis. The 2-36% of EVs that continued to be released caused less transmission to recipient cells, but not on a comparable scale to the reduction of EVs release achieved. CONCLUSION: Up to 98% inhibition of EVs' release was achieved. To prevent the transmission of undesirable phenotypic traits by EVs, their total inhibition may be necessary.

BACKGROUND: Bile duct obstruction is a common issue for patients with advanced cholangiocarcinoma (CCA). Percutaneous transhepatic cholangial drainage (PTCD) is often required to relieve the obstruction. However, PTCD may alter the intestinal microbiota, which can affect the efficacy of immunotherapy. Antibiotics (ATB) can also have significant immunomodulatory effects by perturbing the gut microbiota. Therefore, this study aimed to investigate whether PTCD or ATB therapy is associated with overall survival (OS) or progression-free survival (PFS) in patients with advanced CCA receiving first-line chemotherapy plus immune checkpoint blockade (ICB) in clinical practice. We also explored whether the gut microbiota changes after receiving PTCD. METHODS: We conducted a single-center retrospective analysis of PTCD and ATB therapy in patients with advanced CCA. PTCD was performed before ICB initiation, and ATB was administered within 1 month before and 6 weeks after ICB initiation. Our primary outcomes were PFS and OS. Moreover, we used 16s rRNA sequencing to analyze fecal and bile samples obtained from patients who underwent PTCD. RESULTS: In total, 107 patients with CCA were included. Among patients who did not undergo PTCD, ICB plus chemotherapy significantly improved OS vs. chemotherapy alone (hazard ratio [HR] 0.21, 95% confidence interval [CI] 0.09-0.45, p < 0.0001). PFS was also significantly improved in patients who received ICB plus chemotherapy compared with chemotherapy alone (HR 0.36, 95% CI 0.16-0.80, p = 0.0024). However, ICB plus chemotherapy did not improve survival compared with chemotherapy alone among patients who received PTCD. Overall changes in the fecal microbiota of patients after PTCD involved significant reductions in which Escherichia - Shigella. CONCLUSIONS: The use of ATB or PTCD in patients with CCA receiving ICB was associated with worse OS compared with chemotherapy alone, and PTCD affects the gut microbiota. Escherichia - Shigella was significantly reduced in feces of patients after PTCD.

BACKGROUND: The utilization of modern-immunotherapies, notably immune checkpoint inhibitors (ICIs), has increased markedly in patients with metastatic melanoma over the past decade and are recommended as standard treatment. Given their increasing adoption in routine care for melanoma, understanding patient access to immunotherapy and patterns of its use in Texas is crucial as it remains one of the few states without Medicaid expansion and with high rates of the uninsured population. The objectives of this study were to examine the trend in the utilization of immunotherapy and to determine factors associated with immunotherapy utilization among patients with metastatic melanoma in the era of ICIs in Texas. METHODS: A retrospective cohort study was conducted using the Texas Cancer Registry (TCR) database. The cohort comprised of adult (≥ 18 years) patients with metastatic melanoma diagnosed between June 2011 and December 2018. The trend in immunotherapy utilization was assessed by determining the proportion of patients receiving immunotherapy each year. The Average Annual Percent Change (AAPC) in immunotherapy utilization was assessed using joinpoint regression, while multivariable logistic regression was used to determine the association between patient characteristics and immunotherapy receipt. RESULTS: A total of 1,795 adult patients with metastatic melanoma were identified from the TCR. Immunotherapy utilization was higher among younger patients, those with no comorbidities, and patients with private insurance. Multivariable analysis showed that the likelihood of receipt of immunotherapy decreased with older age [(adjusted Odds Ratio (aOR), 0.92; 95% CI, 0.89- 0.93, p = 0.001], living in high poverty neighborhood (aOR, 0.52; 95% CI, 0.44 - 0.66, p < 0.0001), having Medicaid (aOR, 0.58; 95% CI, 0.44 - 0.73, p = 0.02), being uninsured (aOR, 0.49; 95% CI, 0.31 - 0.64, p = 0.01), and having comorbidities (CCI score 1: aOR, 0.48; 95% CI, 0.34 - 0.71, p = 0.003; CCI score ≥ 2: aOR, 0.32; 95% CI, 0.16 - 0.56, p < 0.0001). CONCLUSIONS AND RELEVANCE: This cohort study identified sociodemographic and socioeconomic disparities in access to immunotherapy in Texas, highlighting the need for policies such as Medicaid expansion that would increase equitable access to this innovative therapy.

BACKGROUND: Recent reports have demonstrated that the entire mitochondrial genome can be secreted in extracellular vesicles (EVs), but the biological attributes of this cell-free mitochondrial DNA (mtDNA) remain insufficiently understood. We used next-generation sequencing to compare plasma EV-derived mtDNA to that of whole blood (WB), peripheral blood mononuclear cells (PBMCs), and formalin-fixed paraffin-embedded (FFPE) tumor tissue from eight rectal cancer patients and WB and fresh-frozen (FF) tumor tissue from eight colon cancer patients. METHODS: Total DNA was isolated before the mtDNA was enriched by PCR with either two primer sets generating two long products or multiple primer sets (for the FFPE tumors), prior to the sequencing. mtDNA diversity was assessed as the total variant number, level of heteroplasmy (mutant mtDNA copies mixed with wild-type copies), variant distribution within the protein-coding genes, and the predicted functional effect of the variants in the different sample types. Differences between groups were compared by paired Student's t-test or ANOVA with Dunnett's multiple comparison tests when comparing matched samples from patients. Mann-Whitney U test was used when comparing differences between the cancer types and patient groups. Pearson correlation analysis was performed. RESULTS: In both cancer types, EV mtDNA presented twice as many variants and had significantly more low-level heteroplasmy than WB mtDNA. The EV mtDNA variants were clustered in the coding regions, and the proportion of EV mtDNA variants that were missense mutations (i.e., estimated to moderately affect the mitochondrial protein function) was significantly higher than in WB and tumor tissues. Nonsense mutations (i.e., estimated to highly affect the mitochondrial protein function) were only observed in the tumor tissues and EVs. CONCLUSION: Taken together, plasma EV mtDNA in CRC patients exhibits a high degree of diversity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01816607 . Registered 22 March 2013.

BACKGROUND: Radioimmunotherapy with cetuximab and conjugates with various radioisotopes is a feasible treatment option for different tumor models. Scandium-47 (47Sc), one of several β--particle-emitting radioisotopes, displays favorable physical and chemical properties for conjugation to monoclonal antibodies. However, the therapeutic efficacy of 47Sc in preclinical and clinical studies is largely unknown. Given that intrinsic alterations in tumors greatly contribute to resistance to anti-epidermal growth factor receptor (EGFR)-targeted therapy, research on overcoming resistance to radioimmunotherapy using cetuximab is required. METHODS: 47Sc was produced by irradiation of a CaCO3 target at the HANARO research reactor in KAERI (Korea Atomic Energy Research Institute) and prepared by chromatographic separation of the irradiated target. Cetuximab was conjugated with 47Sc using the bifunctional chelating agent DTPA. Radiochemical purity was determined using instant thin-layer chromatography. The immunoreactivity of 47Sc-DTPA-cetuximab was evaluated using the Lindmo method and an in vitro cell-binding assay. The inhibitory effects of cetuximab and 47Sc-DTPA-cetuximab were confirmed using cell growth inhibition and BrdU cell proliferation assays. Differences in protein expression levels between cetuximab- and 47Sc-DTPA-cetuximab-treated cells were confirmed using western blotting. Complex formation between RUNX3 and DNA repair components was confirmed using immunoprecipitation and western blotting. RESULTS: Cetuximab induces cell cycle arrest and cell death in EGFR-overexpressing NSCLC cells. Radiolabeling of cetuximab with 47Sc led to increased therapeutic efficacy relative to cetuximab alone. Application of 47Sc-DTPA-cetuximab induced DNA damage responses, and activation of RUNX3 significantly enhanced the therapeutic efficacy of 47Sc-DTPA-cetuximab. RUNX3 mediated susceptibility to EGFR-targeted NSCLC therapy using 47Sc-DTPA-cetuximab via interaction with components of the DNA damage and repair machinery. CONCLUSIONS: 47Sc-DTPA-cetuximab promoted cell death in EGFR-overexpressing NSCLC cells by targeting EGFR and inducing DNA damage as a result of β irradiation emitted from the conjugated 47Sc. Activation of RUNX3 played a key role in DNA damage and repair processes in response to the ionizing radiation and inhibited cell growth, thus leading to more effective tumor suppression. RUNX3 can potentially moderate susceptibility to 47Sc-conjugated cetuximab by modulating DNA damage and repair process mechanisms.

BACKGROUND: Cervical cancer is a preventable and treatable form of cancer yet continues to be the fourth most common cancer among women globally. Primary care is the first point of contact most patients have with health services and is where most cancer prevention and early detection occur. Inadequate follow-up of abnormal test results for cervical abnormalities in primary care can lead to suboptimal patient outcomes including higher mortality and decreased quality of life. AIMS: To explore the magnitude of and factors associated with, inadequate follow-up of test results for cervical abnormalities in primary and ambulatory care. METHODS: MEDLINE, Embase, Cochrane Library and CINAHL were searched for peer-reviewed literature from 2000-2022, excluding case-studies, grey literature, and systematic reviews. Studies were included if they reported on patients aged ≥ 18 years with no previous cancer diagnosis, in a primary care/ambulatory setting. Risk of bias was assessed using the Joanna Briggs Institute Critical appraisal checklists, appropriate to the study design. A segregated methodology was used to perform a narrative synthesis, maintaining the distinction between quantitative and qualitative research. RESULTS: We included 27 publications reporting on 26 studies in our review; all were conducted in high-income countries. They included 265,041 participants from a variety of ambulatory settings such as family medicine, primary care, women's services, and colposcopy clinics. Rates of inadequate follow-up ranged from 4 to 75%. Studies reported 41 different factors associated with inadequate follow-up. Personal factors associated with inadequate follow-up included younger age, lower education, and socioeconomic status. Psychological factors were reported by only 3/26 studies and 2/3 found no significant association. System protective factors included the presence of a regular primary care provider and direct notification of abnormal test results. DISCUSSION: This review describes inadequate follow-up of abnormal cervical abnormalities in primary care. Prevalence varied and the evidence about causal factors is unclear. Most interventions evaluated were effective in decreasing inadequate follow-up. Examples of effective interventions were appointment reminders via telephone, direct notification of laboratory results, and HPV self-sampling. Even though rates of cervical cancer have decreased over the years, there is a lack of information on factors affecting follow-up in primary care and ambulatory settings, particularly in low and middle-income countries. This information is crucial if we are to achieve WHO's interim targets by 2030, and hope to avert 62 million cervical cancer deaths by 2120. TRIAL REGISTRATION: PROSPERO ID CRD42021250136.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common renal malignancy, although newly developing targeted therapy and immunotherapy have been showing promising effects in clinical treatment, the effective biomarkers for immune response prediction are still lacking. The study is to construct a gene signature according to ccRCC immune cells infiltration landscape, thus aiding clinical prediction of patients response to immunotherapy. METHODS: Firstly, ccRCC transcriptome expression profiles from Gene Expression Omnibus (GEO) database as well as immune related genes information from IMMPORT database were combine applied to identify the differently expressed meanwhile immune related candidate genes in ccRCC comparing to normal control samples. Then, based on protein-protein interaction network (PPI) and following module analysis of the candidate genes, a hub gene cluster was further identified for survival analysis. Further, LASSO analysis was applied to construct a signature which was in succession assessed with Kaplan-Meier survival, Cox regression and ROC curve analysis. Moreover, ccRCC patients were divided as high and low-risk groups based on the gene signature followed by the difference estimation of immune treatment response and exploration of related immune cells infiltration by TIDE and Cibersort analysis respectively among the two groups of patients. RESULTS: Based on GEO and IMMPORT databases, a total of 269 differently expressed meanwhile immune related genes in ccRCC were identified, further PPI network and module analysis of the 269 genes highlighted a 46 genes cluster. Next step, Kaplan-Meier and Cox regression analysis of the 46 genes identified 4 genes that were supported to be independent prognosis indicators, and a gene signature was constructed based on the 4 genes. Furthermore, after assessing its prognosis indicating ability by both Kaplan-Meier and Cox regression analysis, immune relation of the signature was evaluated including its association with environment immune score, Immune checkpoint inhibitors expression as well as immune cells infiltration. Together, immune predicting ability of the signature was preliminary explored. CONCLUSIONS: Based on ccRCC genes expression profiles and multiple bioinformatic analysis, a 4 genes containing signature was constructed and the immune regulation of the signature was preliminary explored. Although more detailed experiments and clinical trials are needed before potential clinical use of the signature, the results shall provide meaningful insight into further ccRCC immune researches.

BACKGROUND: In the absence of previous research, we sought to assess the H-Index's predictive significance for radiation-induced trismus (RIT) and osteoradionecrosis of the jaw (ORNJ) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) receiving concurrent chemoradiotherapy (C-CRT). PATIENTS AND METHODS: The research comprised 295 LA-NPC patients who had C-CRT and pre- and post-C-CRT oral exams between June 2010 and December 2021. The H-Index was calculated using neutrophils, monocytes, lymphocytes, hemoglobin, and albumin measurements obtained on the first day of C-CRT. Patients were divided into three and two H-index groups, respectively, based on previously established cutoff values (1.5 and 3.5) and the cutoff value determined by our receiver operating characteristic (ROC) curve analysis. The primary objective was the presence of any significant connections between pretreatment H-Index groups and post-C-CRT RIT and ORNJ rates. RESULTS: RIT and ORNJ was diagnosed in 46 (15.6%) and 13 (7.8%) patients, respectively. The original H-Index grouping could only categorize RIT and ORNJ risks at a cutoff value of 3.5, with no significant differences in RIT and ORNJ rates between groups with H-Index 1.5 and 1.5 to 3.5 (P < 0.05 for each). The ideal H-Index cutoff for both RIT and ORNJ rates was found to be 5.5 in ROC curve analysis, which divided the entire research population into two groups: H-Index ≤ 5.5 (N = 195) and H-Index > 5.5 (N = 110). Intergroup comparisons revealed that patients in the H-Index > 5.5 group had significantly higher rates of either RIT (31.8% vs. 5.9%; P < 0.001) or ORNJ (17.3% vs. 2.2%; P < 0.001) than their H-Index ≤ 5.5 counterparts. The results of the multivariate analysis showed that H-Index > 5.5 was independently linked to significantly higher RIT (P < 0.001) and ORNJ (P < 0.001) rates. CONCLUSION: Pre-C-CRT H-Index > 5.5 is associated with significantly increased RIT and ORNJ rates in LA-NPC patients receiving definitive C-CRT.

BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease, with subtypes that have different clinical behaviours and subsequent prognoses. There is a growing body of evidence suggesting that right-sided colorectal cancer (RCC) and left-sided colorectal cancer (LCC) also differ in treatment success and patient outcomes. Biomarkers that differentiate between RCC and LCC are not well-established. Here, we apply random forest (RF) machine learning methods to identify genomic or microbial biomarkers that differentiate RCC and LCC. METHODS: RNA-seq expression data for 58,677 coding and non-coding human genes and count data for 28,557 human unmapped reads were obtained from 308 patient CRC tumour samples. We created three RF models for datasets of human genes-only, microbes-only, and genes-and-microbes combined. We used a permutation test to identify features of significant importance. Finally, we used differential expression (DE) and paired Wilcoxon-rank sum tests to associate features with a particular side. RESULTS: RF model accuracy scores were 90%, 70%, and 87% with area under curve (AUC) of 0.9, 0.76, and 0.89 for the human genomic, microbial, and combined feature sets, respectively. 15 features were identified as significant in the model of genes-only, 54 microbes in the model of microbes-only, and 28 genes and 18 microbes in the model with genes-and-microbes combined. PRAC1 expression was the most important feature for differentiating RCC and LCC in the genes-only model, with HOXB13, SPAG16, HOXC4, and RNLS also playing a role. Ruminococcus gnavus and Clostridium acetireducens were the most important in the microbial-only model. MYOM3, HOXC4, Coprococcus eutactus, PRAC1, lncRNA AC012531.25, Ruminococcus gnavus, RNLS, HOXC6, SPAG16 and Fusobacterium nucleatum were most important in the combined model. CONCLUSIONS: Many of the identified genes and microbes among all models have previously established associations with CRC. However, the ability of RF models to account for inter-feature relationships within the underlying decision trees may yield a more sensitive and biologically interconnected set of genomic and microbial biomarkers.

BACKGROUND: Recent developments in the field of companion diagnosis and molecular-targeting therapeutic agents have helped in developing treatments targeting human epidermal growth factor receptor 2 (HER2) in gastric cancer (GC) and esophagogastric junction cancer (EGJC), and the importance of accurate diagnosis of HER2 expression is increasing. However, the HER2-positivity rate significantly differs among reports in GC and EGJC, and factors that affect HER2-positivity require elucidation. METHODS: The present study retrospectively examined factors related to HER2-positivity in a single institution, including age, sex, body mass index, the American Society of Anesthesiologists physical status, tumor information, and surgery information, including time to specimen processing. RESULTS: Our study included 165 patients tested for HER2 using GC and EGJC surgery specimens among the 1,320 patients who underwent gastrectomy from January 2007 to June 2022. In total, 35 (21.2%) and 130 (78.8%) patients were HER2-positive and -negative, respectively. Multivariate analysis revealed that intestinal type (odds ratio [OR]: 3.41, 95% confidence interval [CI]: 1.44-8.09, p = 0.005), pM1 (OR: 3.99, 95% CI: 1.51-10.55, p = 0.005), and time to specimen processing of < 120 min (OR: 2.65, 95% CI: 1.01-6.98, p = 0.049) were independent factors that affected HER2-positivity. CONCLUSIONS: The outcomes of the present study indicated that intestinal type, pM, and time to specimen processing are important factors affecting HER2-positive rates in GC and EGJC. Therefore, the risk of false-negative HER2 results may be reduced by decreasing the time required to process the resected specimen. Additionally, accurate diagnosis of HER2 expression may increase the opportunity to administer molecular-targeted drugs that can expect therapeutic effects to patients appropriately. TRAIL REGISTRATION: Retrospectively registered.

BACKGROUND: Ongoing research in the field of both localized, locally advanced and metastatic renal cell carcinoma has resulted in the availability of multiple treatment options. Hence, many questions are still unanswered and await further research. A nationwide collaborative registry allows to collect corresponding data. For this purpose, the Dutch PROspective Renal Cell Carcinoma cohort (PRO-RCC) has been founded, for the prospective collection of long-term clinical data, patient reported outcome measures (PROMs) and patient reported experience measures (PREMs). METHODS: PRO-RCC is designed as a multicenter cohort for all Dutch patients with renal cell carcinoma (RCC). Recruitment will start in the Netherlands in 2023. Importantly, participants may also consent to participation in a 'Trial within cohorts' studies (TwiCs). The TwiCs design provides a method to perform (randomized) interventional studies within the registry. The clinical data collection is embedded in the Netherlands Cancer Registry (NCR). Next to the standardly available data on RCC, additional clinical data will be collected. PROMS entail Health-Related Quality of Life (HRQoL), symptom monitoring with optional ecological momentary assessment (EMA) of pain and fatigue, and optional return to work- and/or nutrition questionnaires. PREMS entail satisfaction with care. Both PROMS and PREMS are collected through the PROFILES registry and are accessible for the patient and the treating physician. TRIAL REGISTRATION: Ethical board approval has been obtained (2021_218) and the study has been registered at ClinicalTrials.gov (NCT05326620). DISCUSSION: PRO-RCC is a nationwide long-term cohort for the collection of real-world clinical data, PROMS and PREMS. By facilitating an infrastructure for the collection of prospective data on RCC, PRO-RCC will contribute to observational research in a real-world study population and prove effectiveness in daily clinical practice. The infrastructure of this cohort also enables that interventional studies can be conducted with the TwiCs design, without the disadvantages of classic RCTs such as slow patient accrual and risk of dropping out after randomization.

BACKGROUND: The impact of sarcopenia on the outcome of patients with left-sided colon and rectal cancer has not been exhaustively investigated. Thus, the present study was performed to evaluate the effect of sarcopenia on the outcome of patients with left-sided colon and rectal cancer. METHODS: Patients with pathologically diagnosed stage I, II and III left-sided colon or rectal cancer who had undergone curative surgery between January 2008 and December 2014 were retrospectively reviewed. The psoas muscle index (PMI) identified by 3D-image analysis of computed tomographic images was the criterion used to diagnose sarcopenia. The cut-off value recommended by Hamaguchi (PMI value < 6.36 cm2/m2 for men and < 3.92 cm2/m2 for women) was adopted to confirm the diagnosis of sarcopenia. According to the PMI, each patient was divided into the sarcopenia group (SG) or the nonsarcopenia group (NSG). Then, the SG was compared with the NSG in terms of postoperative outcomes. RESULTS: Among the 939 patients included, 574 (61.1%) were confirmed to have preoperative sarcopenia. Initially, it was demonstrated that the SG was not significantly different from the NSG in terms of most baseline characteristics except for a lower body mass index (BMI) (P < 0.001), a larger tumour size (P < 0.001) and more weight loss (more than 3 kg in the last three months) (P = 0.033). The SG had a longer hospital stay after surgery (P = 0.040), more intraoperative blood transfusions (P = 0.035), and higher incidence of anastomotic fistula (P = 0.027), surgical site infection (SSI) (P = 0.037) and hypoalbuminemia (P = 0.022), 30-day mortality (P = 0.042) and 90-day mortality (P = 0.041). The SG had significantly worse overall survival (OS) (P = 0.016) and recurrence-free survival (RFS) (P = 0.036) than the NSG. Subsequently, Cox regression analysis revealed that preoperative sarcopenia was an independent predictive factor for worse OS (P = 0.0211, HR = 1.367, 95% CI: 1.049-1.782) and RFS (P = 0.045, HR = 1.299, 95% CI: 1.006-1.677). CONCLUSION: Preoperative sarcopenia adversely affects the outcome of patients with left-sided colon and rectal cancer, and preoperative nutrition supplementation may help us improve their long-term and short-term outcomes.

BACKGROUND: With the availability of health insurance claim data, pharmacovigilance for various drugs has been suggested; however, it is necessary to establish an appropriate analysis method. To detect unintended drug effects and to generate new hypotheses, we conducted a hypothesis-free study to systematically examine the relationship between all prescription nonanticancer drugs and the mortality of colorectal cancer patients. METHODS: We used the Korean National Health Insurance Service-National Sample Cohort database. A total of 2,618 colorectal cancer patients diagnosed between 2004 and 2015 were divided into drug discovery and drug validation sets (1:1) through random sampling. Drugs were classified using the Anatomical Therapeutic Chemical (ATC) classification system: 76 drugs classified as ATC level 2 and 332 drugs classified as ATC level 4 were included in the analysis. We used a Cox proportional hazard model adjusted for sex, age, colorectal cancer treatment, and comorbidities. The relationship between all prescription nonanticancer drugs and the mortality of colorectal cancer patients was analyzed, controlling for multiple comparisons with the false discovery rate. RESULTS: We found that one ATC level-2 drug (drugs that act on the nervous system, including parasympathomimetics, addictive disorder drugs, and antivertigo drugs) showed a protective effect related to colorectal cancer prognosis. At the ATC level 4 classification, 4 drugs were significant: two had a protective effect (anticholinesterases and opioid anesthetics), and the other two had a detrimental effect (magnesium compounds and Pregnen [4] derivatives). CONCLUSIONS: In this hypothesis-free study, we identified four drugs linked to colorectal cancer prognosis. The MWAS method can be useful in real-world data analysis.

BACKGROUND: Associations between reproductive factors and breast cancer (BC) risk vary by molecular subtype (i.e., luminal A, luminal B, HER2, and triple negative/basal-like [TNBC]). In this systematic review and meta-analysis, we summarized the associations between reproductive factors and BC subtypes. METHODS: Studies from 2000 to 2021 were included if BC subtype was examined in relation to one of 11 reproductive risk factors: age at menarche, age at menopause, age at first birth, menopausal status, parity, breastfeeding, oral contraceptive (OC) use, hormone replacement therapy (HRT), pregnancy, years since last birth and abortion. For each reproductive risk factor, BC subtype, and study design (case-control/cohort or case-case), random-effects models were used to estimate pooled relative risks and 95% confidence intervals. RESULTS: A total of 75 studies met the inclusion criteria for systematic review. Among the case-control/cohort studies, later age at menarche and breastfeeding were consistently associated with decreased risk of BC across all subtypes, while later age at menopause, later age of first childbirth, and nulliparity/low parity were associated with increased risk of luminal A, luminal B, and HER2 subtypes. In the case-only analysis, compared to luminal A, postmenopausal status increased the risk of HER2 and TNBC. Associations were less consistent across subtypes for OC and HRT use. CONCLUSION: Identifying common risk factors across BC subtypes can enhance the tailoring of prevention strategies, and risk stratification models can benefit from subtype specificity. Adding breastfeeding status to current BC risk prediction models can enhance predictive ability, given the consistency of the associations across subtypes.

Assessing long-term tumor survival rates is crucial for evaluating the effectiveness of tumor treatment and burden. However, timely assessment of long-term survival in patients with pancreatic cancer is lagging in China. In this study, we applied period analysis to estimate the long-term survival of pancreatic cancer patients using data from four population-based cancer registries in Taizhou city, eastern China. A total of 1121 patients diagnosed with pancreatic cancer between 2004 and 2018 were included. We assessed the 5-year relative survival (RS) using period analysis and further stratified by sex, age at diagnosis, and region. The 5-year RS during 2014-2018 overall reached 18.9% (14.7% for men and 23.3% for women, respectively). A decrease of the 5-year RS from 30.3% to 11.2% was observed in four diagnostic age gradients (< 55, 55-64, 65-74, and > 74 years age groups). The 5-year RS was higher in urban (24.2%) than in rural (17.4%) areas. Moreover, the 5-year RS of pancreatic cancer patients showed an overall increasing trend for the three periods (2004-2008, 2009-2013, and 2014-2018). Our study, using period analysis for the first time in China, provides the latest estimates of the survival of patients with pancreatic cancer, which provides essential evidence for the prevention and intervention of pancreatic cancer. The results also indicate the importance of further applications of the period analysis for more up-to-date and accurate survival estimates.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is one of the most aggressive malignant tumors. Chromobox (CBX) family plays the role of oncogenes in various malignancies. METHODS: The transcriptional and protein levels of CBX family were confirmed by GEPIA, Oncomine, CCLE, and HPA database. Screening of co-expressed genes and gene function enrichment analysis were performed by GeneMANIA and DAVID 6.8. The prognostic value, immune cell infiltration and drug sensitivity analysis of CBX family in DLBCL were performed by Genomicscape, TIMER2.0, and GSCALite database. Confirmatory Tests of CBX family protein expression in DLBCL were performed by immunohistochemistry. RESULTS: The mRNA and protein expressions of CBX1/2/3/5/6 were higher in DLBCL tissues than control groups. Enrichment analysis showed that the functions of CBX family were mainly related to chromatin remodeling, methylation-dependent protein binding, and VEGF signaling pathway. The high mRNA expressions of CBX2/3/5/6 were identified to be associated with short overall survival (OS) in DLBCL patients. Multivariate COX regression indicated that CBX3 was independent prognostic marker. Immune infiltration analysis revealed that the mRNA expressions of CBX family (especially CBX1, CBX5, and CBX6) in DLBCL were significantly correlated with the infiltration of most immune cells (including B cells, CD8 + T cells, CD4 + T cells, neutrophils, monocytes, macrophages, and Treg cells). Meanwhile, there was a strong correlation between the expression levels of CBX1/5/6 and surface markers of immune cells, such as the widely studied PVR-like protein receptor/ligand and PDL-1 immune checkpoint. Notably, our study found that DLBCL cells with CBX1 over-expression were resistant to the common anti-tumor drugs, but CBX2/5 had two polarities. Finally, we confirmed the higher expressions of CBX1/2/3/5/6 in DLBCL tissues compared with control groups by immunohistochemistry. CONCLUSION: We provided a detailed analysis of the relationship between the CBX family and the prognosis of DLBCL. Distinguished from other studies, We found that high mRNA expressions of CBX2/3/5/6 were associated with poor prognosis in DLBCL patients, and Multivariate COX regression indicated that CBX3 was independent prognostic marker. Besides, our study also found an association between the CBX family and anti-tumour drug resistance, and provided a relationship between CBX family expression and immune cell infiltration.

BACKGROUND: Ovarian cancer screening in BRCA1/2 mutation carriers utilizes assessment of carbohydrate antigen 125 (CA125) and transvaginal ultrasound (TVU), despite low sensitivity and specificity. We evaluated the association between CA125 levels, BRCA1/2 mutation status and menopausal status to provide more information on clinical conditions that may influence CA125 levels. METHODS: We retrospectively analyzed repeated measurements of CA125 levels and clinical data of 466 women at high risk for ovarian cancer. CA125 levels were compared between women with and without deleterious mutations in BRCA1/2. Pearson's correlation was used to determine the association between age and CA125 serum level. Differences in CA125 levels were assessed with the Mann-Whitney U test. The effect of BRCA1/2 mutation status and menopausal status on the change in CA125 levels was determined by Two-factor analysis of variance (ANOVA). RESULTS: The CA125 serum levels of premenopausal women (median, 13.8 kU/mL; range, 9.4 - 19.5 kU/mL) were significantly higher than in postmenopausal women (median, 10.4 kU/mL; range, 7.7 - 14.0 kU/mL; p < .001). There was no significant difference in the CA125 levels of BRCA mutation carriers and non-mutation carriers across all age groups (p = .612). When investigating the combined effect of BRCA1/2 mutation and menopausal status, variance analysis revealed a significant interaction between BRCA1/2 mutation status and menopausal status on CA125 levels (p < .001). There was a significant difference between the CA125 levels of premenopausal and postmenopausal women, with a large effect in BRCA mutation carriers (p < .001, d = 1.05), whereas in non-mutation carriers there was only a small effect (p < .001, d = 0.32). CONCLUSION: Our findings suggest that hereditary mutations in BRCA1/2 affect the decline of CA125 levels with increasing age. To prove a definite effect of this mutation on the CA125 level, prospective trials need to be conducted to define new cut-off levels of CA 125 in mutation carriers and optimize ovarian cancer screening.

BACKGROUND: Even though chemotherapy-induced nausea and vomiting (CINV) can be well controlled in the acute phase, the incidence of delayed CINV remains high. In this study, we intend to investigate whether prolonged use of NK-1 receptor antagonist (RA) in addition to 5-HT3 RA and dexamethasone (DEX) was more effective in preventing delayed CINV. METHODS: This randomised, open-label, controlled study was designed to compare the efficacy and safety of fosaprepitant 150 mg given on days 1,3 (prolonged group) versus on day 1 (regular group) in patients receiving highly emetogenic chemotherapy (HEC). All patients also treated with palonosetron on day 1 and DEX on days 1-3. The primary endpoint was the incidence of delayed nausea and vomiting. The second endpoint was AEs. All the above endpoints were defined according to CTCAE 5.0. RESULTS: Seventy-seven patients were randomly assigned to prolonged group and seventy-nine to regular group. Prolonged group demonstrated superiority in controlling delayed CINV to regular group, with statistically significant lower incidence of nausea (6.17% vs 12.66%, P = 0.0056), and slightly lower incidence of grade 1 vomiting (1.62% vs 3.80%, P = 0.0953) in the delayed phase. In addition, prolonged use of fosaprepitant was safe. No significant difference was found between the two groups regarding constipation, diarrhea, hiccough, fatigue, palpitation and headache in delayed phase. CONCLUSIONS: Prolonged use of fosaprepitant can effectively and safely prevent delayed CINV in patients receiving HEC.

PURPOSE: To assess the clinical characteristics and the risk factors related to the unfavorable prognosis of endometrioid ovarian carcinoma (EOVC) based on data from the Surveillance, Epidemiology, and End Results (SEER) database and two clinical centers in China. METHODS: Data were extracted from the SEER database and two clinical centers in China (2010 ~ 2021), 884 cases and 87 patients with EOVC were selected, respectively. Overall survival (OS) and progression-free survival (PFS) were compared among the different groups using Kaplan-Meier analysis. The Cox proportional-hazards model was used to identify independent prognostic factors related to EOVC. A nomogram was constructed based on the risk factors of the SEER database affecting prognosis and the discrimination and calibration of the nomogram were evaluated by C-index and calibration curves. RESULTS: The average age at diagnosis of patients with EOVC in the SEER database and two centers in China was 55.77 ± 12.40 years and 47.14 ± 11.50 years, 84.7% and 66.6% of them were diagnosed at FIGO stage I ~ II, respectively. In the SEER database, age over 70 years, advanced FIGO stage, tumor grade 3, only unilateral salpingo-oophorectomy were independent risk factors of unfavorable prognosis. In two clinical centers in China, 27.6% of EOVC patients were diagnosed with synchronous endometriosis. Advanced FIGO stage, HE4 > 179 pmol/L and bilateral ovarian involvement significantly correlated with poor OS and PFS in Kaplan-Meier analysis. Body mass index (BMI) < 19.34 kg/m2 was an independent risk factor relating to OS and PFS. Additionally, C-index of internal and external verification for the nomogram were 0.812 and 0.754 respectively, revealing good accuracy and clinical applicability. CONCLUSIONS: Most patients were diagnosed at early stage, low grade and had better prognosis. Asian/Pacific Islander and Chinese diagnosed with EOVC were more likely to be younger than whites and blacks. Age, tumor grade and FIGO stage (SEER database) and BMI (two centers) are independent prognostic factors. HE4 appears to be more valuable in prognostic assessment compared with CA125. The nomogram had good discrimination and calibration for predicting prognosis, providing a convenient and reliable tool for clinical decision-making for patients with EOVC.