Multi-omics association study identifies new potential prostate cancer- causing gene

Abstract

BACKGROUND Prostate cancer is one of the most common malignant tumors among men worldwide, and surgery remains its mainstay of treatment. It is unclear how prostate cancer develops and what the most effective drug targets are for treating prostate cancer. Therefore, we sought to identify the genes responsible for the pathogenesis of prostate cancer. METHODS By integrating multidimensional and high-throughput data, proteome wide association studies (PWAS), transcriptome wide association studies (TWAS), single-cell sequencing, functional enrichment, Mendelian randomization (MR), and Bayesian co-localization analyses were used to screen for candidate genes that may contribute to prostate cancer and associate with clinical results of prostate cancer. RESULTS Our comprehensive analysis showed that protein abundance of eight genes was associated with prostate cancer, four of which were validated at the transcriptome level. These 8 candidate genes (MSMB, PLG, CHMP2B, ATF6B, EGF, TAPBP, GAS1 and MMP7) were validated. After combining single-cell sequencing, Mendelian randomization, and Bayesian co-localization analyses, we identified 1 gene (TAPBP) that is strongly associated with prostate cancer and explored the potential mechanisms of its pathogenicity and its clinical relevance.