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A single centre experience of patients with rare cancers referred for early phase clinical trials.
IF 3.4 2区 医学
BMC Cancer Pub Date : 2025-03-28 DOI: 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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951660/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association of HLA-A*02:01 type with efficacy and toxicity of immune checkpoint inhibitor therapy in melanoma patients: a retrospective cohort study.
IF 3.4 2区 医学
BMC Cancer Pub Date : 2025-03-28 DOI: 10.1186/s12885-025-13857-y
Isabel Manger, Christina Schmitt, Carola Berking, Lars E French, Julio Vera-Gonzalez, Lucie Heinzerling
{"title":"Association of HLA-A*02:01 type with efficacy and toxicity of immune checkpoint inhibitor therapy in melanoma patients: a retrospective cohort study.","authors":"Isabel Manger, Christina Schmitt, Carola Berking, Lars E French, Julio Vera-Gonzalez, Lucie Heinzerling","doi":"10.1186/s12885-025-13857-y","DOIUrl":"https://doi.org/10.1186/s12885-025-13857-y","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICI) are highly effective but may induce severe or even fatal and unpredictable immune-related adverse events (irAEs). It is unclear whether human leukocyte antigen (HLA) genes contribute to the susceptibility of developing irAEs during ICI therapy.</p><p><strong>Methods: </strong>This multicentre retrospective study investigated the association of irAE and outcome with HLA-A*02:01 status in a cohort of 97 patients with metastatic melanoma undergoing ICI therapy. Organ-specific irAEs and therapy outcome as assessed by response rate, progression-free survival (PFS) and overall survival (OS) were analysed depending on HLA type HLA-A*02:01. For the outcome only patients with cutaneous melanoma were analysed. Chi square test, exact fisher test, Kruskal Wallis test and log rank test were employed for statistical analysis (p ≤ 0.05).</p><p><strong>Results: </strong>The cohort included 38 HLA-A*02:01 positive (39.2%) and 59 HLA-A*02:01 negative (60.8%) patients. Data showed no evidence of an association of HLA-A*02:01 with organ-specific irAEs except for a numerical difference in immune-related colitis. Furthermore, response rates of the subgroup of patients with metastatic cutaneous melanoma did not differ between the two cohorts. The median PFS was 5 months and 8 months in HLA-A*02:01 positive and negative patients with cutaneous melanoma, respectively.</p><p><strong>Conclusion: </strong>HLA-A*02:01 was not associated with specific checkpoint inhibitor-induced organ toxicity in this cohort of HLA-A-typed melanoma patients. Interestingly, in the relatively small subgroup of patients with cutaneous melanoma an earlier progression in HLA-A*02:01 positive patients was observed, however not in the long term. These findings are exploratory due to the limited sample size and require validation in larger, prospective cohorts.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"565"},"PeriodicalIF":3.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PD-1 inhibitors improve the efficacy of transcatheter arterial chemoembolization combined with apatinib in advanced hepatocellular carcinoma: a meta-analysis and trial sequential analysis.
IF 3.4 2区 医学
BMC Cancer Pub Date : 2025-03-28 DOI: 10.1186/s12885-025-13932-4
Jiahui Yu, Jinxin Yu, Yimiao Chen, Yuting Yang, Pengsheng Yi
{"title":"PD-1 inhibitors improve the efficacy of transcatheter arterial chemoembolization combined with apatinib in advanced hepatocellular carcinoma: a meta-analysis and trial sequential analysis.","authors":"Jiahui Yu, Jinxin Yu, Yimiao Chen, Yuting Yang, Pengsheng Yi","doi":"10.1186/s12885-025-13932-4","DOIUrl":"https://doi.org/10.1186/s12885-025-13932-4","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of adding programmed death-1 (PD-1) inhibitors to transcatheter arterial chemoembolization (TACE) combined with apatinib for advanced hepatocellular carcinoma (HCC) remains controversial. This study aimed to evaluate the efficacy of incorporating PD-1 inhibitors into TACE combined with apatinib.</p><p><strong>Methods: </strong>Relevant literature on TACE combined with apatinib plus PD-1 inhibitors for advanced HCC was searched in PubMed, Cochrane Library, Embase, and Web of Science databases. Trial sequential analysis (TSA) was conducted to minimize randomization errors and assess whether the meta-analysis provided conclusive evidence.</p><p><strong>Results: </strong>Six studies involving 1,452 patients were included. Compared with the TACE combined with apatinib treatment group (T-A), TACE combined with apatinib plus PD-1 inhibitors (T-A-P) significantly prolonged overall survival (OS) (Hazard Ratio [HR] 2.22, 95% Confidence Interval [CI] 1.93-2.56; p < 0.001) and progression-free survival (PFS) (HR 2.36, 95% CI 2.01-2.77; p < 0.001), while also improving the objective response rate (ORR) (risk ratios [RR] 1.60, 95% CI 1.20-2.14; p < 0.001) and disease control rate (DCR) (RR 1.06, 95% CI 1.00-1.12; p < 0.001). TSA results indicated that additional studies were required to confirm the significance of DCR. Prognostic analysis identified treatment regimen and extrahepatic metastasis as common independent risk factors for OS and PFS. The incidence of adverse events in the T-A-P treatment group was comparable to that in the T-A treatment group.</p><p><strong>Conclusion: </strong>Adding PD-1 inhibitors to TACE combined with apatinib significantly prolonged OS and PFS, particularly in patients without extrahepatic metastases. It also improved ORR and DCR in patients with HCC.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"564"},"PeriodicalIF":3.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Long-term outcomes and prognostic factors of eye-preserving treatment with particle beam radiotherapy for orbital malignancies.
IF 3.4 2区 医学
BMC Cancer Pub Date : 2025-03-28 DOI: 10.1186/s12885-025-13986-4
Weixu Hu, Qiong Cai, Jing Gao, Jiyi Hu, Qingting Huang, Haojiong Zhang, Lin Kong
{"title":"Long-term outcomes and prognostic factors of eye-preserving treatment with particle beam radiotherapy for orbital malignancies.","authors":"Weixu Hu, Qiong Cai, Jing Gao, Jiyi Hu, Qingting Huang, Haojiong Zhang, Lin Kong","doi":"10.1186/s12885-025-13986-4","DOIUrl":"https://doi.org/10.1186/s12885-025-13986-4","url":null,"abstract":"<p><strong>Background: </strong>This retrospective study report the clinical experience of eye-preserving treatment follow by particle beam radiotherapy (IMPT or CIRT) for orbital malignancies. And to evaluate prognostic factors for orbital and lacrimal gland tumors.</p><p><strong>Methods: </strong>Sixty-two patients with orbital malignancies were identified in the records of a single center between 2015 and 2021. Sixty-one patients met inclusion criteria. All of the patients received eye-preserving treatment before PBRT. Majority of the patients (91.8%) were treatment with CIRT. Clinical data, treatment modality, local control, metastases and survivals and visual outcomes, as well as associated prognostic indicators were were assessed.</p><p><strong>Results: </strong>Sixty-one patients were followed with a median of 40.7 months (44.3 months for surviving patients). The 3- and 5-year DSS and LC rates were 88.1% and 69.9%, and the 3- and 5-year DMC rates were 77.5% and 74.2% for entire orbital malignancies. For lacrimal gland carcinoma, the 5-year DSS, LC, DMC, and PFS rates were 83.3%, 64.8%, 66.8%, and 53.4%. Tumor size, T stage, extraorbital invasion, and bone invasion influenced survivals. No grade 3 or higher acute toxicities were observed. A total of 8 patients experienced grade 3-4 visual impairment.</p><p><strong>Conclusions: </strong>Particle radiotherapy following eye-preserving treatment provided a favorable local control and survivals with moderate acute and late toxicities, even in patients with unresectable disease. Particle radiotherapy was a promising strategy for management of orbital tumors.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"569"},"PeriodicalIF":3.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Analysis of extracellular vesicles of frequently used colorectal cancer cell lines.
IF 3.4 2区 医学
BMC Cancer Pub Date : 2025-03-27 DOI: 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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951637/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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).
IF 3.4 2区 医学
BMC Cancer Pub Date : 2025-03-27 DOI: 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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948765/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rectal prolapse as an initial presentation of colorectal cancer: a systematic review.
IF 3.4 2区 医学
BMC Cancer Pub Date : 2025-03-27 DOI: 10.1186/s12885-025-13924-4
Fatemeh Shahabi, Abbas Abdollahi, Mahdieh Zarif-Sadeghian, Dorin Ziyaie, Ehsan Rahimpour, Majid Ansari, Esmat Davoudi-Monfared
{"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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948720/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhancing prediction and stratifying risk: machine learning and bayesian-learning models for catheter-related thrombosis in chemotherapy patients.
IF 3.4 2区 医学
BMC Cancer Pub Date : 2025-03-27 DOI: 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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948715/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
RBMS1-HSPA8 axis activation drives head and neck squamous cell carcinoma progression.
IF 3.4 2区 医学
BMC Cancer Pub Date : 2025-03-27 DOI: 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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948914/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Estrogen receptor α suppresses hepatocellular carcinoma by restricting M2 macrophage infiltration through the YAP-CCL2 axis.
IF 3.4 2区 医学
BMC Cancer Pub Date : 2025-03-27 DOI: 10.1186/s12885-025-13676-1
De-Hua Wang, Dong-Wei He, Ting-Ting Lv, Xiao-Kuan Zhang, Zi-Jie Li, Zhi-Yu Wang
{"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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948847/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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