Genetic relationships between gut microbiota and prostate cancer: Mendelian Randomization combined with Bioinformatics Analysis

Background. Prostate cancer (PCa) is a leading cause of male cancer-related death globally. While gut microbiota is linked to PCa, their genetic association remains unclear.Methods. We screened genetic instruments related to gut microbiota and paired them with PCa genome-wide association study data to conduct Mendelian randomization (MR) analysis. Positive MR findings were then subjected to colocalization analysis. Subsequently, we utilized the Gene Expression Omnibus (GEO) data set to perform differential expression analysis, aiming to identify differentially expressed associated genes (DEAGs). We determined the importance scores of these DEAGs through four machine learning models and constructed a nomogram based on these findings, and then validated it in another group of the GEO data set.Results. MR analysis found 16 gut bacteria causally linked to PCa (7 risk, 9 protective), with 144 related genes. PLCL1, VSNL1, ROR2, NRXN3, and TEAD1 were identified as feature genes for constructing the nomogram that provides a quantitative prediction of the risk of PCa onset.Conclusions. This study indicates that there are causal links between gut microbiota and PCa. Feature genes may affect the occurrence, development, and prognosis of prostate cancer by inhibiting the epithelial-mesenchymal transition, proliferation, migration, and invasion of cells.