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

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.