Identifying the causal role and therapeutic potential of immune-related genes in bladder cancer: a Mendelian randomization study.

IF 2.9 4区医学 Q3 ENDOCRINOLOGY & METABOLISM

Discover. Oncology Pub Date : 2025-10-13 DOI:10.1007/s12672-025-03806-3

Yonggang Chen, Qingfeng Yu, Xiaomei Jiang, Lin Li, Le Kang

{"title":"Identifying the causal role and therapeutic potential of immune-related genes in bladder cancer: a Mendelian randomization study.","authors":"Yonggang Chen, Qingfeng Yu, Xiaomei Jiang, Lin Li, Le Kang","doi":"10.1007/s12672-025-03806-3","DOIUrl":null,"url":null,"abstract":"Background: Bladder cancer, a highly aggressive malignancy, necessitates effective therapeutic strategies due to the significant correlation between muscle invasion and prognosis. Despite advancements in immunotherapy, the mechanisms through which immune-related genes influence bladder cancer remain unclear.Methods: We conducted a comprehensive causal analysis of immune-related genes using GWAS data from the UK Biobank and FinnGen, and immune gene information from InnateDB. Mendelian Randomization (MR) analysis, supported by sensitivity, colocalization, and reverse causality analyses, was performed using eQTLGen Consortium and proteomics GWAS data. We analyzed protein-protein interaction networks with GeneMANIA and validated findings using mRNA expression and clinical survival data from the TCGA database.Results: The expression of the GSTM1 gene demonstrated an inverse correlation with cancer risk, suggesting a protective role in disease progression. Our study also identified OLFM4, NTN1, ITPR3, CLU, and CARD11 as genes significantly associated with immune cell composition and bladder cancer survival. Additionally, we uncovered protein interaction networks and key pathways involving these immune-related genes, providing new insights into bladder cancer intervention and treatment.Conclusion: This study elucidates the immune-related pathways influencing bladder cancer, highlighting GSTM1 and other key immune-related genes as potential biomarkers. These discoveries pave the way for innovative therapeutic approaches, advancing personalized medicine strategies in bladder cancer treatment.","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1857"},"PeriodicalIF":2.9000,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12518733/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Discover. Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12672-025-03806-3","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Bladder cancer, a highly aggressive malignancy, necessitates effective therapeutic strategies due to the significant correlation between muscle invasion and prognosis. Despite advancements in immunotherapy, the mechanisms through which immune-related genes influence bladder cancer remain unclear.

Methods: We conducted a comprehensive causal analysis of immune-related genes using GWAS data from the UK Biobank and FinnGen, and immune gene information from InnateDB. Mendelian Randomization (MR) analysis, supported by sensitivity, colocalization, and reverse causality analyses, was performed using eQTLGen Consortium and proteomics GWAS data. We analyzed protein-protein interaction networks with GeneMANIA and validated findings using mRNA expression and clinical survival data from the TCGA database.

Results: The expression of the GSTM1 gene demonstrated an inverse correlation with cancer risk, suggesting a protective role in disease progression. Our study also identified OLFM4, NTN1, ITPR3, CLU, and CARD11 as genes significantly associated with immune cell composition and bladder cancer survival. Additionally, we uncovered protein interaction networks and key pathways involving these immune-related genes, providing new insights into bladder cancer intervention and treatment.

Conclusion: This study elucidates the immune-related pathways influencing bladder cancer, highlighting GSTM1 and other key immune-related genes as potential biomarkers. These discoveries pave the way for innovative therapeutic approaches, advancing personalized medicine strategies in bladder cancer treatment.

Abstract Image

查看原文本刊更多论文

确定膀胱癌免疫相关基因的因果作用和治疗潜力：一项孟德尔随机研究。

背景：膀胱癌是一种高度侵袭性的恶性肿瘤，由于其肌肉侵犯与预后有显著相关性，因此需要有效的治疗策略。尽管免疫治疗取得了进展，但免疫相关基因影响膀胱癌的机制仍不清楚。方法：我们使用来自UK Biobank和FinnGen的GWAS数据以及来自InnateDB的免疫基因信息，对免疫相关基因进行了全面的因果分析。使用eQTLGen Consortium和蛋白质组学GWAS数据进行孟德尔随机化（MR）分析，并辅以敏感性、共定位和反向因果分析。我们利用GeneMANIA分析了蛋白-蛋白相互作用网络，并利用TCGA数据库中的mRNA表达和临床生存数据验证了研究结果。结果：GSTM1基因的表达与癌症风险呈负相关，表明其在疾病进展中具有保护作用。我们的研究还发现OLFM4、NTN1、ITPR3、CLU和CARD11是与免疫细胞组成和膀胱癌存活显著相关的基因。此外，我们发现了涉及这些免疫相关基因的蛋白质相互作用网络和关键途径，为膀胱癌的干预和治疗提供了新的见解。结论：本研究阐明了影响膀胱癌的免疫相关通路，突出了GSTM1等关键免疫相关基因作为潜在的生物标志物。这些发现为创新治疗方法铺平了道路，推进了膀胱癌治疗的个性化药物策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊