Systematic Elucidation of the Aneuploidy Landscape and Identification of Aneuploidy Driver Genes in Prostate Cancer

Abstract

Aneuploidy is widely identified as a remarkable feature of malignancy genomes. Increasing evidences suggested aneuploidy was involved in the progression and metastasis of prostate cancer (PCa). Nevertheless, no comprehensive analysis was conducted in PCa about the effects of aneuploidy on different omics and, especially, about the driver genes of aneuploidy. Here, we validated the association of aneuploidy with the progression and prognosis of PCa and performed a systematic analysis in mutation profile, methylation profile, and gene expression profile, which detailed the molecular process aneuploidy implicated. By multi-omics analysis, we managed to identify 11 potential aneuploidy driver genes (GSTM2, HAAO, C2orf88, CYP27A1, FAXDC2, HFE, C8orf88, GSTP1, EFS, HIF3A, and WFDC2), all of which were related to the development and metastasis of PCa. Meanwhile, we also found aneuploidy and its driver genes were correlated with the immune microenvironment of PCa. Our findings could shed light on the tumorigenesis of PCa and provide a better understanding of the development and metastasis of PCa; additionally, the driver genes could be promising and actionable therapeutic targets pointing to aneuploidy.