Mp41-01 Uncovering Somatic Genetic Susceptibility Factors in Prostate Cancer Through Comprehensive Genome-Wide Analysis

You have accessJournal of UrologyProstate Cancer: Markers I (MP41)1 May 2024MP41-01 UNCOVERING SOMATIC GENETIC SUSCEPTIBILITY FACTORS IN PROSTATE CANCER THROUGH COMPREHENSIVE GENOME-WIDE ANALYSIS Lede Lin, Kan Wu, and Xiang Li Lede LinLede Lin , Kan WuKan Wu , and Xiang LiXiang Li View All Author Informationhttps://doi.org/10.1097/01.JU.0001008896.93851.5b.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Given that hereditary prostate cancer (PCa) accounts for only a small fraction of PCa phenotypes, there is still a substantial journey ahead in exploring the somatic genetic susceptibility factors contributing to sporadic PCa. METHODS: The expression quantitative trait loci (eQTLs) data were sourced from the GTEx dataset for prostate-specific genes, and the summary statistic information was collected for 5854 genes. Genetic associations with PCa were extracted from three well-established consortiums: the UK Biobank (9131 cases and 173493 controls), the PRACTICAL study (79148 cases and 61106 controls) and the FinnGen cohort (13216 cases and 119948 controls). To prioritize potential causal targets, additional analysis, including the protein-protein interaction (PPI), The Cancer Genome Atlas (TCGA) dataset and the single-cell-type expression analysis, were performed. RESULTS: Generally, a total of 150 common significant genes with the same causal association with PCa were identified. Out of the 150 genes examined, 67.33% (101/150) were found to have protein-coding functions, while only 30.67% (46/150) of these genes had prior mentions in the scientific literature. Notably, the analysis of TCGA dataset showed that only 44.67% (67/150) of the genes produced consistent results with the Mendelian randomization (MR) analysis. Furthermore, the evaluation of single-cell RNA-seq data and colocalization analysis singled out MSMB as a critical gene associated with the occurrence of PCa. CONCLUSIONS: We pinpointed a range of prostate-specific genes that display causal associations with the onset of PCa. Among these, the MSMB gene emerged as a pivotal factor linked to PCa, demonstrating robust consistency across all four assessments, including the MR, TCGA dataset, single-cell RNA-seq data and colocalization analysis. These findings provided fresh perspectives on the pathogenesis of PCa and presented potential targets for drug development. Source of Funding: Not applicable © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e673 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Lede Lin More articles by this author Kan Wu More articles by this author Xiang Li More articles by this author Expand All Advertisement PDF downloadLoading ...