BMC Cancer最新文献

{"title":"In situ phenotypic and karyotypic co-detection of aneuploid TCs and TECs in cytological specimens with abnormal cervical screening results.","authors":"Yanling Wang, Alexander Y Lin, Daisy Dandan Wang, Peter Ping Lin, Xuexin Zhou, Yongbin Yang, Yaping Zhu","doi":"10.1186/s12885-025-14346-y","DOIUrl":"10.1186/s12885-025-14346-y","url":null,"abstract":"<p><strong>Background: </strong>To distinguish and co-detect aneuploid CD31^- tumor cells (TCs) and CD31⁺ tumor endothelial cells (TECs) may have significant diagnostic values for cervical cancer screening. However, there are very few relevant studies. In the present study, a novel \"immunofluorescence staining integrated with fluorescence in situ hybridization (iFISH)\" tumor tissue biopsy platform was applied to comprehensively investigate the clinical utilities of aneuploid TCs and TECs in all-stage cervical lesion smear specimens.</p><p><strong>Methods: </strong>A total of 196 patients were enrolled in this study. Immunofluorescence staining of p16 and Ki67 combined with FISH was applied to quantitatively co-detect and characterize subcategorized aneuploid CD31^- TCs and CD31⁺ TECs in cervical cytological specimens. The Kruskal‒Wallis H test was used to compare the distributions of aneuploid TCs and TECs among all stages of cervical lesions and among the different high-risk HPV types (HPV16/18 and non-HPV16/18). The diagnostic value of detecting aneuploid TCs and TECs for high-grade squamous intraepithelial lesions (HSIL⁺) was investigated via receiver operating characteristic curve analysis.</p><p><strong>Results: </strong>The number of total aneuploid CD31^- TCs and their p16⁺ and/or Ki67⁺ (p16/Ki67⁺) subtypes increased markedly with the severity of cervical lesions, although a similar trend was not observed for aneuploid CD31⁺ TECs. The increase in aneuploid TCs resulted from HPV16/18 infection was mainly concentrated in low-grade squamous intraepithelial lesion(LSIL), whereas the increase caused by non-HPV16/18 infection was mainly concentrated in HSIL. To identify HSIL⁺, the area under the curve (AUC) of tetraploid TCs was the largest (0.739), followed by multiploid (≥ pentaploid) TCs (0.724) and triploid TCs (0.699). For the combined subtypes, the AUC of ≥ tetraploid TCs was 0.745, and their unique diagnostic value was clinically reflected by their high specificity.</p><p><strong>Conclusion: </strong>The quantity of CD31^- aneuploid TCs was associated with the severity of cervical lesions. In HPV16/18 positive patients, aneuploid CD31^- TCs were significantly increased in the LSIL. Moreover, aneuploid CD31^- TCs exhibited remarkable specificity for detecting HSIL⁺. Further studies are required to expand the potential clinical utility of detecting CD31^- aneuploid TCs.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"945"},"PeriodicalIF":3.4,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149362","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}

{"title":"Innovations in modern low-LET radiotherapy regimens for locally advanced non-small cell lung cancer: a meta-analysis and systematic review of high-dose-rate brachytherapy, stereotactic body radiotherapy, and hypofractionated proton therapy.","authors":"Mingyu Tan, Lu Li, Bangxian Tan, Jinxin Yang","doi":"10.1186/s12885-025-14328-0","DOIUrl":"10.1186/s12885-025-14328-0","url":null,"abstract":"<p><strong>Background: </strong>This study assesses recent treatments for locally advanced non-small cell lung cancer (LA-NSCLC) ineligible for surgery, comparing high-dose-rate (HDR) brachytherapy with conventional low linear energy transfer (LET) hypofractionated radiotherapy methods.</p><p><strong>Methods: </strong>From 9435 papers, 8 meeting criteria were selected, covering 484 LA-NSCLC patients (2005-2019). Analysis focused on comparing outcomes, exploring biologically effective doses (BED), and examining toxicities.</p><p><strong>Results: </strong>HDR brachytherapy had better effectiveness. Specific data revealed that the median overall survival (OS) with HDR brachytherapy was 38 months, with a significant 2-year OS rate of 68.0% (95% CI, 58.2-79.4%). In comparison, stereotactic body radiation (SBRT) and proton treatment had 2-year OS rates of 54% (95% CI, 36-71%), and 56% (95% CI, 42-70%), respectively. In terms of local control (LC), the 2-year LC rate for HDR brachytherapy stood at 87.1% (95% CI, 79-95%), whereas the 2-year LC rates for SBRT and proton therapy were 75% (95% CI, 63-86%) and 84% (95% CI, 68 -100%), respectively. The 2-year OS for BED₁₀ equal to or greater than 78 Gy was 62% (95% CI, 51-72%), compared to 38% (95% CI, 17-58%) for BED₁₀ less than 78 Gy. Acute toxicity was lower with HDR brachytherapy (95% CI, 0-10%) versus SBRT (95% CI, 8-16%), with no grade 3 + events reported for proton therapy. Furthermore, the rate of late toxicity events above grade 3 was 3% (95% CI, 0-6%) for SBRT and 14% (95% CI, 4-24%) for proton therapy, while no late toxicities above grade 3 were observed with brachytherapy.</p><p><strong>Conclusions: </strong>Hypofractionated low LET irradiation is efficacious and safe for LA-NSCLC, while HDR brachytherapy provides significant OS and LC advantages with few toxicities. Achieving BED₁₀ ≥ 78 Gy significantly impacts OS. These findings guide clinical practice and stimulate further LA-NSCLC treatment advancements.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"942"},"PeriodicalIF":3.4,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149390","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}

{"title":"Phase I study of the safety, tolerability, and potential therapeutic dose of OMT-110 for patients with refractory metastatic Colorectal Cancer.","authors":"Youngbae Jeon, MinJeong Jung, BongHwang Jeong, Haejun Lee, Sun Jin Sym, Jeong-Heum Baek","doi":"10.1186/s12885-025-14351-1","DOIUrl":"10.1186/s12885-025-14351-1","url":null,"abstract":"<p><strong>Background: </strong>OMT-110 is a repositioned drug candidate for the treatment of metastatic colorectal cancer (mCRC). This phase I study aimed to determine the appropriate dose of OMT-110 for phase II trials and its safety, tolerability, and efficacy. We conducted the first-in-human dose-escalation study of patients with advanced mCRC (age 20 years or older) who had refractory disease.</p><p><strong>Methods: </strong>OMT-110 was administered subcutaneously in a repeated cycle of 21 days on/seven days off until tumor progression, toxicity, or withdrawal. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria ver4.03. The pharmacokinetic profiles were determined before and after OMT-110 administration. Pharmacodynamic and efficacy evaluations were performed using abdominopelvic computed tomography (APCT), chest CT, and ¹⁸F-FDG-Positron emission tomography/CT, following the Response Evaluation Criteria in Solid Tumors v1.1. Fourteen patients were divided into four cohorts to receive doses ranging from 12.5 mg to 100 mg daily.</p><p><strong>Results: </strong>Based on our results, a daily dose of 100 mg is recommended following a repeated 28-day treatment cycle of 21 days on/seven days off. Of the 54 adverse events experienced by the participants in the safety set, all were grade 1 or 2, except for two serious adverse events. OMT-110 was either \"unrelated\" or \"definitely not related\" or \"probably unrelated\" to these events. Pharmacokinetic analysis revealed no apparent accumulation.</p><p><strong>Conclusions: </strong>Based on the evaluation of pharmacodynamic and efficacy parameters, OMT-110 is a promising novel systemic therapy with potential immunomodulatory effects for patients with advanced mCRC.</p><p><strong>Trial registration: </strong>CRIS Registration Number KCT0005336 (first posted on 08/08/2017).</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"937"},"PeriodicalIF":3.4,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141353","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}

{"title":"Discovery of homocamptothecin derivative TOP-0618 as a radiosensitive agent for the treatment of pancreatic cancer.","authors":"Yin Tang, Chengyi Huang, Di Chen, Yangyang Gong, Liang Chen, Wenjuan Chen, Liang You, Zhenyuan Miao, Huojun Zhang","doi":"10.1186/s12885-025-14347-x","DOIUrl":"10.1186/s12885-025-14347-x","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer is one of the most lethal malignancies characterized by a complex tumor microenvironment (TME) and highly heterogeneous nature, making it resistant to radiotherapy. This study aims to evaluate the radiosensitizing effect of homocamptothecin derivative TOP-0618 on pancreatic cancer.</p><p><strong>Methods: </strong>Clonogenic assays and cell viability assays were used to evaluate the radiosensitizing effects of TOP-0618 on pancreatic cancer cells. Cell cycle and apoptosis were detected using flow cytometry. A pancreatic bi-flank xenograft tumor model was used to evaluate the radiosensitivity of TOP-0618. H&E staining analyses and TUNEL staining were used to examine necrosis and apoptosis of pancreatic xenograft tumors.</p><p><strong>Results: </strong>Cytotoxicity assays revealed that IC₅₀ values of TOP-0618 against PANC-1 and MIAPaCa-2 cells were 1.442 µmol/L and 1.198 µmol /L, respectively. Additionally, clonogenic assays revealed that TOP-0618 exerted radiosensitizing effects on both pancreatic cells, and the sensitizer enhancement ratio (SER) of TOP-0618 was 1.14 for the PANC-1 cell line and 1.65 for the MIAPaCa-2 cell line. The preliminary study revealed that TOP-0618 improved radiosensitivity by enhancing G2/M phase arrest and increasing the apoptosis of pancreatic cells. Subsequently, in a pancreatic bi-flank xenograft tumor model, TOP-0618 combined with irradiation significantly inhibited tumor growth, and increased necrosis and apoptosis in pancreatic xenograft tumors.</p><p><strong>Conclusions: </strong>Our work demonstrates the radiosensitizing effect of homocamptothecin derivative TOP-0618 on pancreatic cancer both in vivo and vitro, and lays a foundation for clinical transformation.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"936"},"PeriodicalIF":3.4,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141268","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}

{"title":"Efficacy and safety of combining tislelizumab with capecitabine compared to capecitabine alone in the adjuvant treatment of biliary tract cancers: rationale and protocol design for a randomized clinical trial.","authors":"Xubiao Wei, Yabo Jiang, Jinxue Zhou, Hongkun Zhou, Dong Qu, Xiaofei Ye, Yaxin Zheng, Shuqun Cheng","doi":"10.1186/s12885-025-14367-7","DOIUrl":"10.1186/s12885-025-14367-7","url":null,"abstract":"<p><strong>Background: </strong>Adjuvant therapy with capecitabine is recommended to improve survival for resectable biliary tract cancers (BTC) patients. Considering that the combination of PD-1/PD-L1 inhibitors with chemotherapy has demonstrated a survival benefit over chemotherapy alone in advanced stage BTC, we aim to evaluate the treatment efficacy and safety of tislelizumab, a PD-1 inhibitor, combined with capecitabine vs. capecitabine alone as an adjuvant treatment in patients with resectable BTC.</p><p><strong>Method: </strong>This multicenter randomized controlled study will include a total of 140 patients who will have undergone curative resection within 4 weeks prior to enrollment and will have been pathologically diagnosed with cholangiocarcinoma (including intrahepatic and extrahepatic cholangiocarcinoma) or muscle-invasive gallbladder carcinoma. Those patients will be randomly assigned 1:1 to tislelizumab combined with capecitabine or capecitabine alone group. The primary endpoint will be recurrence free survival (RFS), the secondary endpoints will be overall survival (OS) and adverse events (AEs). Multi-omics biomarkers will be assessed as exploratory objective.</p><p><strong>Discussion: </strong>There remains a major unmet need for more effective adjuvant therapies for resectable BTC. If this study demonstrates that adding tislelizumab enhances the therapeutic efficacy of capecitabine, this combined regimen will potentially improve the prognosis of patients with resectable BTC. In addition, we will analyze the relationship between various gene expression profiles and clinical endpoint events to define the ideal patient population receiving adjuvant immunotherapy.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"938"},"PeriodicalIF":3.4,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141439","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}

{"title":"MicroRNAs involved in colorectal cancer, a rapid mini-systematic review.","authors":"Sogol Shirzad, Majid Eterafi, Zeinab Karimi, Mahdi Barazesh","doi":"10.1186/s12885-025-14343-1","DOIUrl":"10.1186/s12885-025-14343-1","url":null,"abstract":"<p><strong>Introduction: </strong>Colorectal cancer (CRC) involves the uncontrolled proliferation of glandular epithelial cells in the colon or rectum. The high mortality rate associated with CRC has driven extensive research into innovative diagnostic and therapeutic strategies. Among these, microRNAs (miRNA) have gained attention for their crucial role in regulating various cellular processes that contribute to the initiation, progression, and metastasis of CRC.</p><p><strong>Method: </strong>This systematic review aimed to assess the roles of various miRNAs in CRC by analyzing multiple studies. The PICO framework was followed to structure the study regarding miRNA involved in CRC development and progression compared to normal cases. The outcomes were measured according miRNAs impact on CRC progression, survival rates, and treatment response. Systematic review of studies published from 2000 to November 2023 were included. Data were collected from prominent databases, including Google Scholar, PubMed, ScienceDirect, Irandoc, SID, and Magiran, covering studies from 2000 to November 2023. Studies were managed using EndNote for citation management, and duplicates were removed. The remaining studies were evaluated based on predefined inclusion and exclusion criteria.</p><p><strong>Results: </strong>In our review, we categorized 28 miRNAs based on their potential tumor suppressor or oncogenic effects in CRC progression. Among them, 14 miRNAs were highlighted as important based on the assessment using TCGA data, with miR-200a also showing a significant effect on patient survival.</p><p><strong>Conclusion: </strong>This study compiled and analyzed validated miRNAs associated with CRC progression. The findings suggest the potential of these miRNAs as non-invasive biomarkers, which may be used alone or in combination with traditional tumor markers for improved diagnostic and prognostic applications in CRC. This review contributes novel insights by updating the current understanding and offering a comprehensive evaluation of miRNAs in CRC.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"934"},"PeriodicalIF":3.4,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141440","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}

{"title":"Clinical benefit of continuation of PD-1 inhibitors after progression on first-line chemoimmunotherapy in metastatic gastric cancer and biomarker exploration.","authors":"Mengwei Zhang, Long Bai, Jianwen Chen, Qi Meng, Yunxin Lu, Dongsheng Zhang","doi":"10.1186/s12885-025-14286-7","DOIUrl":"10.1186/s12885-025-14286-7","url":null,"abstract":"<p><strong>Background: </strong>Whether continuing immunotherapy after progression in second-line settings of metastatic gastric cancer (MGC) remains unclear. Herein, we explored the efficacy of PD-1 inhibitors for MGC after progression on previous chemoimmunotherapy.</p><p><strong>Methods: </strong>We retrospectively identified MGC patients who received oxaliplatin-based chemotherapy plus PD-1 inhibitor, with or without trastuzumab, as first-line treatment. The patients received treatment with or without PD-1 inhibitors beyond progression in patients with MGC were divided into treatment beyond progression (TBP) group and non-TBP (NTBP) group. The median progression free survival (PFS) and overall survival (OS) from the start of treatment after progression were assessed.</p><p><strong>Results: </strong>The mOS and mPFS in the TBP group was significantly longer than that in the NTBP group (mOS: 9.0 vs. 5.0 months, P = 0.011; mPFS: 4.3 vs. 2.7 months, P = 0.03). Moreover, TBP was an independent prognostic factor for both PFS and OS in multivariate analysis. In the subgroup analysis, patients who were male, had a favorable ECOG (0-1), classified into diffuse histologic subtype and achieved disease control in the prior chemoimmunotherapy, might be more likely to benefit from continuing immunotherapy compared to discontinuation beyond progression.</p><p><strong>Conclusion: </strong>PD-1 inhibitors based therapeutic strategy may be a reasonable option in second-line setting for MGC who progressed on prior immunotherapy. Further larger prospective trials are warranted to validate these findings.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"935"},"PeriodicalIF":3.4,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141262","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}

{"title":"Clinical prediction of pathological complete response in breast cancer: a machine learning study.","authors":"Chongwu He, Tenghua Yu, Liu Yang, Longbo He, Jin Zhu, Jing Chen","doi":"10.1186/s12885-025-14335-1","DOIUrl":"10.1186/s12885-025-14335-1","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to develop and validate machine learning models to predict pathological complete response (pCR) after neoadjuvant therapy in patients with breast cancer patients.</p><p><strong>Methods: </strong>Clinical and pathological data from 1143 patients were analyzed, encompassing variables such as age, gender, marital status, histologic grade, T stage, N stage, months from diagnosis to treatment, molecular subtype, and response to neoadjuvant therapy. Seven machine learning models were trained and validated using both internal and external datasets. Model performance was evaluated using multiple metrics, and interpretability analysis was conducted to assess feature importance.</p><p><strong>Results: </strong>Key variables influencing pCR included grade, N stage, months from diagnosis to treatment, and molecular subtype. The Naive Bayes model emerged as the most effective, with accuracy (0.746), sensitivity (0.699), specificity (0.808), and F1 score (0.759) surpassing other models. Both internal and external validation confirmed the model's robust predictive power. A web tool was developed for clinical use, aiding in personalized treatment planning. Interpretability analysis further elucidated the contribution of features to pCR prediction, enhancing clinical applicability.</p><p><strong>Conclusion: </strong>The Naive Bayes model provides a robust tool for personalized treatment decisions in patients with breast cancer undergoing neoadjuvant therapy. By accurately predicting pCR rates, it enables clinicians to tailor treatment strategies, potentially improving outcomes.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"933"},"PeriodicalIF":3.4,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131805","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}

{"title":"Correction: Hospital factors and metastatic surgery in colorectal cancer patients, a population-based cohort study.","authors":"Malin Ljunggren, Caroline E Dietrich, Emma Rosander, Gabriella Palmer, Bengt Glimelius, Anna Martling, Caroline Nordenvall","doi":"10.1186/s12885-025-14339-x","DOIUrl":"10.1186/s12885-025-14339-x","url":null,"abstract":"","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"929"},"PeriodicalIF":3.4,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131810","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}

{"title":"Causal role of immune cells in primary liver cancer: a mendelian randomization study.","authors":"Jia Liu, Tongyuan Zhang, Yang Gao, Dong Ji, Lijian Chen","doi":"10.1186/s12885-025-14327-1","DOIUrl":"10.1186/s12885-025-14327-1","url":null,"abstract":"<p><strong>Background: </strong>Primary liver cancer is one of the most common fatal malignancies worldwide. Observational studies have shown that immune cells are closely linked to primary liver cancer, however, due to issues like reverse causality and confounding variables, the causal direction and extent of this association remain unclear. Thus, this study aimed to explore the potential causal association between immune cells and primary liver cancer, encompassing hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).</p><p><strong>Methods: </strong>A two-sample mendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWAS) of the 731 immune traits and primary liver cancer. The primary liver cancer dataset consisted of a total of 456,348 subjects, with 123 cases of HCC and 456,225 controls, as well as 104 cases of ICC and 456,244 controls, all of European ancestry. The primary method for assessing causality was inverse variance weighting (IVW), with sensitivity analysis utilized for testing heterogeneity and pleiotropy.</p><p><strong>Results: </strong>Two immunophenotypes were significantly associated with HCC risk: CD3 on CD45RA + CD4+ (OR [95% CI]: 1.334 [1.077 to 1.651], p = 0.008), CD80 on monocyte (OR [95% CI]: 0.578 [0.397 to 0.844], p = 0.004). Additionally, six immunophenotypes were identified to be significantly associated with the risk of ICC: SSC-A on NK (OR [95% CI]: 1.685 [1.166 to 2.436], p = 0.006); CD3 on CD28- CD8br: (OR [95% CI]: 1.826 [1.206 to 2.766], p = 0.004); CD45RA on naive CD4+: (OR [95% CI]: 1.391 [1.119 to 1.729], p = 0.003); Resting Treg %CD4: (OR [95% CI]: 1.290 [1.069 to 1.558], p = 0.008); HLA DR on HSC: (OR [95% CI]: 0.539 [0.343 to 0.846], p = 0.007); Plasmacytoid DC %DC: (OR [95% CI]: 0.610 [0.462 to 0.806], p < 0.001). And sensitivity analyses confirmed the robustness of the main findings.</p><p><strong>Conclusions: </strong>MR analysis has revealed the causal relationship between immune cells and primary liver cancer through genetic methods. These findings could assist in clinical decision-making and provide new directions for the treatment and research of primary liver cancer.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"928"},"PeriodicalIF":3.4,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131783","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}