BMC CancerPub Date : 2025-03-28DOI: 10.1186/s12885-025-13934-2
Angelos Angelakas, Natalie Cook, Donna M Graham, Matthew Krebs, Fiona Thistlethwaite, Louise Carter
{"title":"A single centre experience of patients with rare cancers referred for early phase clinical trials.","authors":"Angelos Angelakas, Natalie Cook, Donna M Graham, Matthew Krebs, Fiona Thistlethwaite, Louise Carter","doi":"10.1186/s12885-025-13934-2","DOIUrl":"https://doi.org/10.1186/s12885-025-13934-2","url":null,"abstract":"<p><strong>Background: </strong>Cancers affecting < 6/100,000/year are classified as rare, but they account for up to 25% of all cancers and are associated with worse 5-year survival than common cancers. Early-phase clinical trials (EPCTs) may represent a viable treatment option for patients with rare cancers as they have evolved significantly with novel designs and the increasing use of precision medicine.</p><p><strong>Methods: </strong>A retrospective study of patients with rare cancers referred to a large EPCT team at a UK specialist centre over 5 years (2016-2020) was conducted. Patient demographics, medical and oncological history, genomic variants, EPCT participation, responses and survival outcomes were analysed.</p><p><strong>Results: </strong>In total, 240 patients with rare cancers were included. The mean age at diagnosis was 51.7 years (range 16-84), 54.2% of the patients were female. The most frequent rare cancers originated from the digestive system (27.1%), female genital tract (20%) and head and neck (H + N) (18.3%). Molecular profiling was offered to 45.5% of the population, median number of gene alterations was 3 per patient (range 1-20) while actionable gene alterations were reported in 60.2% (n = 50) of those with identified gene aberrations. Fifty-one patients participated in EPCTs, with 39.2% achieving SD and 11.8% PR. Median PFS for trial participants was three months (95% CI 1.12 - 4.88) while median OS in the trial patients was 16 months (95% CI 9.10 - 22.90) compared to 7 months for non-trial participants (95% CI 5.50 - 8.51). Finally, poor Royal Marsden Hospital (RMH) prognostic score (2-3) was correlated with worse survival when controlling for age and sex (HR 1.714, 95% CI 1.19 - 2.46, p = 0.004).</p><p><strong>Conclusions: </strong>Participation of patients with rare cancers in EPCTs may be associated with a survival benefit and lead to the development of new treatments for these patients. Moreover, expanded use of precision medicine is paramount as it can inform targeted treatment selection in this heterogenous group.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"558"},"PeriodicalIF":3.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC CancerPub Date : 2025-03-27DOI: 10.1186/s12885-025-13936-0
Marie Boudná, Nicolas Blavet, Tetiana Samoilenko, Táňa Macháčková, Robin Jugas, Petra Vychytilová-Faltejsková, Miroslav Boudný, Renata Bartošová, Jan Kotouček, Vojtěch Bystrý, Kateřina Koželková, Ondřej Slabý, Kamila Součková
{"title":"Analysis of extracellular vesicles of frequently used colorectal cancer cell lines.","authors":"Marie Boudná, Nicolas Blavet, Tetiana Samoilenko, Táňa Macháčková, Robin Jugas, Petra Vychytilová-Faltejsková, Miroslav Boudný, Renata Bartošová, Jan Kotouček, Vojtěch Bystrý, Kateřina Koželková, Ondřej Slabý, Kamila Součková","doi":"10.1186/s12885-025-13936-0","DOIUrl":"https://doi.org/10.1186/s12885-025-13936-0","url":null,"abstract":"<p><p>Colorectal cancer (CRC) ranks as the second most prevalent malignancy globally, highlighting the urgent need for more effective diagnostic and therapeutic strategies, as well as a deeper understanding of its molecular basis. Extensive research has demonstrated that cells actively secrete extracellular vesicles (EVs) to mediate intercellular communication at both proximal and distal sites. In this study, we conducted a comprehensive analysis of the RNA content of small extracellular vesicles (sEVs) secreted into the culture media of five frequently utilised CRC cell lines (RKO, HCT116, HCT15, HT29, and DLD1). RNA sequencing data revealed significant insights into the RNA profiles of these sEVs, identifying nine protein-coding genes and fourteen long non-coding RNA (lncRNA) genes that consistently ranked among the top 30 most abundant across all cell lines. Notably, the genes found in sEVs were highly similar among the cell lines, indicating a conserved molecular signature. Several of these genes have been previously documented in the context of cancer biology, while others represent novel discoveries. These findings provide valuable insights into the molecular cargo of sEVs in CRC, potentially unveiling novel biomarkers and therapeutic targets.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"555"},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC CancerPub Date : 2025-03-27DOI: 10.1186/s12885-025-13913-7
Vianney Bastit, Justine Lequesne, Alexandra Leconte, Sophie Deneuve, Francois Mouawad, Elske Quak, Corinne Jeanne, Bénédicte Clarisse, Juliette Thariat
{"title":"Effectiveness of bilateral tongue base mucosectomy by transoral robotic surgery or transoral laser microsurgery in combination with tonsillectomy in identifying head and neck primary cancer of unknown primary: a randomized phase 2 protocol (RoboCUP trial).","authors":"Vianney Bastit, Justine Lequesne, Alexandra Leconte, Sophie Deneuve, Francois Mouawad, Elske Quak, Corinne Jeanne, Bénédicte Clarisse, Juliette Thariat","doi":"10.1186/s12885-025-13913-7","DOIUrl":"https://doi.org/10.1186/s12885-025-13913-7","url":null,"abstract":"<p><strong>Background: </strong>In cases of prevalent lymphadenopathy in the head and neck cancer region, identifying the primary tumor site allows for more precise radiotherapy targeting. This improves treatment by reducing the volumes of mucosal irradiation and potentially lowering morbidity. An extensive diagnostic workup, including FDG PET-CT imaging and bilateral tonsillectomy, has been shown to identify the primary cancer in 60% of cases. Mucosectomy of the tongue base holds promise for detecting additional primary sites. When performed using minimally invasive endoscopic techniques such as transoral robotic surgery (TORS) or transoral laser microsurgery (TLM), mucosectomy results in minimal morbidity. However, the effectiveness of tongue base mucosectomy in detecting primary tumors has yet to be evaluated in a randomized trial involving patients with lymphadenopathy of unknown primary.</p><p><strong>Methods: </strong>The RoboCUP trial is a multicentre, open-label, randomized, non-comparative phase 2 trial aiming to evaluate the benefit of bilateral TORS or TLM-assisted tongue base mucosectomy in association to tonsillectomy in the assessment of prevalent cervical lymphadenopathy with a negative exhaustive diagnostic workup. The main endpoint is the proportion of patients with detection of a primary cancer. Surgery will consist in tongue base mucosectomy plus tonsillectomy in the experimental arm, and the standard of care, i.e. tonsillectomy alone in the control arm. Patients will then be treated by intensity modulated radiotherapy, possibly with chemotherapy as radiosensitizer, per current guidelines. Using a single-stage Fleming design, 36 patients will be enrolled in the experimental arm, and 36 patients in the control arm.</p><p><strong>Discussion: </strong>This trial aims to improve the diagnostic performances, i.e. detection of primary tumor, in patients with head and neck carcinoma of unknown primary. It is expected that the subsequent therapeutic changes could enhance radiotherapy accuracy, and could improve the prognosis, toxicity profiles and quality-of-life of patients.</p><p><strong>Trial registration: </strong>NCT04767048, registered February, 19, 2021.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"551"},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rectal prolapse as an initial presentation of colorectal cancer: a systematic review.","authors":"Fatemeh Shahabi, Abbas Abdollahi, Mahdieh Zarif-Sadeghian, Dorin Ziyaie, Ehsan Rahimpour, Majid Ansari, Esmat Davoudi-Monfared","doi":"10.1186/s12885-025-13924-4","DOIUrl":"https://doi.org/10.1186/s12885-025-13924-4","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer rising incidence still pose a public health challenge. In the present systematic review, we aimed to study the colorectal cancer patients with initial presentation of rectal prolapse.</p><p><strong>Method: </strong>The study protocol was developed (PROSPERO CRD42017060473). We searched Web of Science, PubMed and Scopus to identify case reports of rectal Prolapse as a chief compliant of colorectal cancer. The Preferred Reporting Items for Systematic Reviews and Meta- Analysis (PRISMA) guidelines were used for screening and data extraction.</p><p><strong>Results: </strong>Thirty-one case reports were included in this review. More than half of the patients were females over 65 years old and mean ± SD age of the cases were 64 ± 17.9 years and, the female gender were mentioned in 17 (56%) case reports. The majority (64.5%) of the identified cancer belong to rectum and recto-sigmoid origin's location. In the history retained from the cases, rectal bleeding and constipation were the most frequent reported accompanied symptoms in colorectal cancer cases with initial presentation of rectal prolapse. 67.7% of all identified cases in this review published at 2015 and later.</p><p><strong>Conclusion: </strong>Rectal prolapse can be an initial presentation of colorectal cancer, which is more prevalent in female more than 65 years old. The most common symptoms accompanied rectal prolapse were rectal bleeding and constipation. According to rising published case reports on colorectal cancer patients with initial presentation of rectal prolapse in recent years, further work-up is recommended for patients without predisposing factors for a concomitant tumor.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"553"},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC CancerPub Date : 2025-03-27DOI: 10.1186/s12885-025-13946-y
Tao An, Han Han, Junying Xie, Yifan Wang, Yiqi Zhao, Hao Jia, Yanfeng Wang
{"title":"Enhancing prediction and stratifying risk: machine learning and bayesian-learning models for catheter-related thrombosis in chemotherapy patients.","authors":"Tao An, Han Han, Junying Xie, Yifan Wang, Yiqi Zhao, Hao Jia, Yanfeng Wang","doi":"10.1186/s12885-025-13946-y","DOIUrl":"https://doi.org/10.1186/s12885-025-13946-y","url":null,"abstract":"<p><strong>Background: </strong>Catheter-related thrombosis (CRT) is a serious complication in cancer patients undergoing chemotherapy, yet existing risk prediction models demonstrate limited accuracy. This study aimed to evaluate the clinical utility of machine learning (ML) and Bayesian-learning models for CRT prediction in a large cohort of breast cancer patients undergoing catheterization.</p><p><strong>Methods: </strong>A total of 3337 breast cancer patients with central venous catheters (Cohort 1) were included to develop and test ML models. Given the suboptimal clinical feasibility of ML models, the Bayesian-learning model was constructed using odds ratio analysis and Gaussian distribution. The hazard ratio for the high-risk and low-risk groups was calculated using Cox proportional hazards regression analysis, and the model was validated in an independent cohort of 1274 patients (Cohort 2).</p><p><strong>Results: </strong>In Cohort 1, 246 patients (7.37%) developed CRT. Among the eight ML algorithms tested, WeightedEnsemble model exhibited relatively stable performance, achieving area under the receiver operating characteristic curves of 0.89 in the training set and 0.69 in the test set. WeightedEnsemble improved generalization by integrating multiple base models. The odds ratio analysis and Bayesian-learning modeling identified 4 independent risk factors: hemoglobin (threshold point [TP]: 134.63 g/L), activated partial thromboplastin time (TP: 31.71 s), total cholesterol (TP: 11.19 mmol/L), and catheterization approach (TP: peripherally inserted central catheters). A simplified risk stratification system was developed, categorizing patients into low-risk (0-1 factors) and high-risk (2-4 factors) groups. This system exhibited strong CRT risk discriminative ability, as confirmed through survival analysis (P < 0.001 in both cohorts). In Cohort 1, cox regression analysis showed that the high-risk group had hazard ratio (HR) of 1.60 (95% confidence interval [CI], 1.15-2.22) for both catheter indwelling time and catheter use duration. In Cohort 2, the system maintained stable discriminative ability, with an HR of 5.63 (95% CI, 3.46-9.21) for catheter indwelling time and 5.62 (95% CI, 3.46-9.12) for catheter use duration.</p><p><strong>Conclusions: </strong>While ML models demonstrated high predictive performance, their clinical applicability was limited due to complexity. The Bayesian-learning-based risk stratification model provided a simplified yet robust alternative, effectively predicting CRT risk and offering a clinically feasible tool for risk assessment in breast cancer patients with chemotherapy. Further validation in diverse cancer populations is warranted to refine its generalizability.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"552"},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Estrogen receptor α suppresses hepatocellular carcinoma by restricting M2 macrophage infiltration through the YAP-CCL2 axis.","authors":"De-Hua Wang, Dong-Wei He, Ting-Ting Lv, Xiao-Kuan Zhang, Zi-Jie Li, Zhi-Yu Wang","doi":"10.1186/s12885-025-13676-1","DOIUrl":"https://doi.org/10.1186/s12885-025-13676-1","url":null,"abstract":"<p><strong>Purpose: </strong>Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with significant differences in incidence and outcomes between men and women. Estrogen receptor alpha (ERα) expression is associated with sex-based differences and poor prognostic outcomes in HCC. However, the detailed function of ERα in the tumor microenvironment of HCC remains unclear.</p><p><strong>Methods: </strong>Bioinformatics analysis of differentially expressed genes in HCC samples was performed from publicly available databases, and ERα was selected. The function of ERα was examined in the cell experiments. A co-culture system was built to study function of ERα-treated liver cells on macrophages in vitro. The precise mechanism was determined using quantitative real-time PCR, western blotting, immunohistochemistry, mass spectrometry, co-immunoprecipitation, and dual-luciferase reporter assay.</p><p><strong>Results: </strong>ERα played an important role in the pathogenesis of sexual dimorphism in HCC. ERα mainly acted on macrophages in the tumor microenvironment (TME) of HCC and reduced M2 macrophage infiltration through CCL2. By acting on NF2 and 14-3-3theta, ERα enhanced YAP phosphorylation and attenuated the nuclear translocation of YAP, thereby suppressing CCL2 expression. It also acted as a transcription factor that regulated CCL2 expression at the transcriptional level.</p><p><strong>Conclusion: </strong>ERα/YAP/CCL2 signaling reduced M2 macrophages infiltration to inhibit HCC progression, revealing the effect of ERα in cancer cells on immune cells in HCC microenvironment.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"550"},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC CancerPub Date : 2025-03-27DOI: 10.1186/s12885-025-13937-z
Xinghong Yin, Meng Luo, Xiaojun Zha, Maoli Duan, Yehai Liu
{"title":"RBMS1-HSPA8 axis activation drives head and neck squamous cell carcinoma progression.","authors":"Xinghong Yin, Meng Luo, Xiaojun Zha, Maoli Duan, Yehai Liu","doi":"10.1186/s12885-025-13937-z","DOIUrl":"10.1186/s12885-025-13937-z","url":null,"abstract":"<p><strong>Background: </strong>Head and Neck Squamous Cell Carcinoma (HNSCC) presents significant challenges in terms of treatment and prognosis, highlighting the urgent need for new therapeutic targets and the development of effective targeted therapies to enhance patient outcomes and survival.</p><p><strong>Methods: </strong>The expression level of RBMS1 in HNSCC was identified by GEO and TCGA databases through systematic bioinformatics analysis, and further verified in human specimens by quantitative Real-time PCR, Western blot, and immunohistochemistry. The results of CCK-8, colony formation assay, wound healing, Transwell, and tumor formation assays in nude mice showed that RBMS1 promoted the proliferation, migration, and invasion of HNSCC cells. The downstream target genes of RBMS1 were identified in the RBMS1 knockdown and the control groups of TU177 cells using RNA sequencing. HSPA8 was identified as a downstream target gene of RBMS1 in functional in vitro and tumor formation experiments in nude mice.</p><p><strong>Results: </strong>Elevated expression levels of RBMS1 in HNSCC were identified using relevant databases and validated in human specimens. In both in vitro and in vivo studies, overexpression of RBMS1 promoted the proliferation, migration, and invasion of HNSCC cells, whereas knockdown of RBMS1 significantly inhibited these processes. RNA sequencing analysis revealed HSPA8 as a downstream target of RBMS1, and rescue experiments confirmed that HSPA8 serves as a crucial intermediary in the regulatory pathway of tumor progression influenced by RBMS1.</p><p><strong>Conclusions: </strong>This study suggests that RBMS1 regulates HSPA8 to promote the proliferation, migration, and invasion of HNSCC cells, making it a potential therapeutic target for HNSCC.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"549"},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC CancerPub Date : 2025-03-27DOI: 10.1186/s12885-025-13968-6
Weimin Xie, Zhangyi Wang, Xiaohang Liu, Songhong Tan
{"title":"Robotic single site versus robotic multiport hysterectomy in endometrial cancer: a systematic review and meta-analysis.","authors":"Weimin Xie, Zhangyi Wang, Xiaohang Liu, Songhong Tan","doi":"10.1186/s12885-025-13968-6","DOIUrl":"https://doi.org/10.1186/s12885-025-13968-6","url":null,"abstract":"<p><strong>Objective: </strong>This meta-analysis aims to compare the safety and efficacy of robotic single-site hysterectomy (RSSH) with robotic multiport hysterectomy (RMPH) in treating endometrial cancer.</p><p><strong>Methods: </strong>We conducted a comprehensive literature search across several databases, including PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, the Chinese National Knowledge Infrastructure (CNKI), Wan Fang, and the Chinese Science and Technology Journal Full Text Database (VIP). The search covered literature from inception until October 17, 2024. The primary outcomes included intraoperative complications, postoperative complications, postoperative pain scores, and satisfaction with cosmetic outcomes. The secondary outcomes included operative time (min), estimated blood loss (ml), hemoglobin drop, blood transfusion, conversion, postoperative hospital stay, lymph nodes harvested, sentinel lymph node identification, recurrence, and mortality during follow-up. Data analysis was performed using random-effects or fixed-effects models, calculating combined risk ratios (RR), weighted mean difference (WMD), and 95% confidence intervals (95% CI).</p><p><strong>Results: </strong>Five studies describing a total of 448 patients were retained and included for this meta-analysis. No significant differences were found between RSSH and RMPH regarding intraoperative complications, postoperative complications, and postoperative pain scores. There were also no differences in terms of operation time, estimated blood loss, hemoglobin drop, blood transfusion, conversion, postoperative hospital stay, lymph nodes harvested, and sentinel lymph node identification.</p><p><strong>Conclusion: </strong>This systematic review and meta-analysis provides evidence that RSSH is effective and safe for the treatment of endometrial cancer, as it is generally equivalent to RMPH regarding perioperative outcomes.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"554"},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC CancerPub Date : 2025-03-27DOI: 10.1186/s12885-025-13976-6
Yuxin Wang, Lu Xie, Ye Gu, Hangbin Jin, Jianfeng Yang, Qiang Liu, Xiaofeng Zhang
{"title":"Complex interplay between type 2 diabetes mellitus and pancreatic cancer: insights from observational and mendelian randomization analyses.","authors":"Yuxin Wang, Lu Xie, Ye Gu, Hangbin Jin, Jianfeng Yang, Qiang Liu, Xiaofeng Zhang","doi":"10.1186/s12885-025-13976-6","DOIUrl":"https://doi.org/10.1186/s12885-025-13976-6","url":null,"abstract":"<p><strong>Background: </strong>To investigate the causal relationship between type 2 diabetes mellitus (T2DM), pancreatic cancer (PC) risk and identify the mediating effects of various risk factors on that relationship.</p><p><strong>Methods: </strong>581 PC patients and 582 healthy controls who visited our center from January 2013 to December 2023 were included in this retrospective study. Multivariable logistic regression was performed to evaluate the association between T2DM and PC through odds ratios (ORs) and 95% confidence intervals (CIs). Mendelian randomization (MR) studies were then conducted to explore the causal relationship between T2DM and PC, and causal mediation analysis (CMA) to examine the mediating role of common risk factors.</p><p><strong>Results: </strong>After adjusting for confounding factors, retrospective analysis revealed significant association between new-onset diabetes mellitus (NODM) and PC risk, with insulin treatment also linked to increased PC development. The standard inverse-variance weighted (IVW) method indicated that genetic susceptibility to T2DM was associated with an increased risk of developing PC (OR = 1.11; 95% CI = 1.034-1.193). Furthermore, MR showed T2DM, insulin treatment, FGF-4, and sulfhydryl oxidase 2 may be independently associated with the prevalence of PC. Specially, CMA demonstrated that insulin treatment, FGF4, and sulfhydryl oxidase 2 mediate the pathway from T2DM to PC, contributing 56.8%, 55.8%, and 5.9% of the total effect, respectively.</p><p><strong>Conclusion: </strong>This study supports the association between T2DM, specifically NODM, and increased PC risk, with insulin therapy, FGF4, and sulfhydryl oxidase 2 mediating this pathway. Further research is required to elucidate the mechanisms underlying these mediating effects.</p><p><strong>Clinical trial number: </strong>not applicable.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"556"},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC CancerPub Date : 2025-03-27DOI: 10.1186/s12885-025-13948-w
Song Wang, Jianran Guo, Xinmiao Xian, Min Li, Anqi Zhang, Yujiao Liu, Yifei Zhang, Shen Chen, Guohao Gu, Xuehua Zhang, Dong Yan, Meng An, Li Pan, Bo Fu
{"title":"Distinct 5-methylcytosine profiles of LncRNA in breast cancer brain metastasis.","authors":"Song Wang, Jianran Guo, Xinmiao Xian, Min Li, Anqi Zhang, Yujiao Liu, Yifei Zhang, Shen Chen, Guohao Gu, Xuehua Zhang, Dong Yan, Meng An, Li Pan, Bo Fu","doi":"10.1186/s12885-025-13948-w","DOIUrl":"https://doi.org/10.1186/s12885-025-13948-w","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have identified a complex relationship between methylation patterns and the development of various cancers. Breast cancer (BC) is the second leading cause of cancer mortality among women. Approximately 5-20% of BC patients are at risk of BC brain metastases (BCBM). Although 5-methylcytosine (m5C) has been identified as an important regulatory modifier, its distribution in BCBM is not well understood. This study aimed to investigate the distribution of m5C in BCBM.</p><p><strong>Materials and methods: </strong>Samples from BCBM (231-BR cells) and BC (MDA-MB-231 cells) groups were subjected to a comprehensive analysis of the m5C methylation in long non-coding RNA (lncRNA) using methylated RNA immunoprecipitation next-generation sequencing (MeRIP-seq). The expression levels of methylated genes in BC and adjacent tissues were verified through quantitative real-time polymerase chain reaction (RT-qPCR). Enrichment pathway analyses were through Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to predict the potential functions of m5C in BCBM.</p><p><strong>Results: </strong>The MeRIP-seq analysis identified 23,934 m5C peaks in BCBM and 21,236 m5C in BC. A total of 9,480 annotated genes (BCBM) and 8,481 annotated genes (BC) were mapped. Notably, 1,819 methylation sites in lncRNA were upregulated in BCBM, whereas 2,415 methylation sites were upregulated in BC. Significant m5C hypermethylated lncRNAs included ENST00000477316, ENST00000478098 and uc002gtt.1, whereas hypomethylated lncRNAs included ENST00000600912, ENST00000493668, ENST00000544651 and ENST00000464989. These results were verified by qPCR and MeRIP-qPCR in BC and BCBM. Considering the strong association between m5C RNA methylation regulators and lncRNA, we examined the expression levels of 13 m5C RNA methylation regulators and observed significant differences between BC tissues and adjacent normal tissues. In addition, the interaction between regulators of altered expression and the differentially expressed genes in vitro was analyzed. The GO and KEGG pathways analyses revealed that genes significantly associated with m5C sites in lncRNA were linked to the BCBM signaling pathways.</p><p><strong>Conclusion: </strong>This uncovered significant variations in the levels and distribution of m5C in BCBM compared to BC. The findings provide a new theoretical understanding of the mechanisms of BCBM.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"557"},"PeriodicalIF":3.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}