In-silico identification of frequently mutated genes and their co-enriched metabolic pathways associated with Prostate cancer progression

Prostate cancer (PCa) has emerged as a significant health burden in men globally. Several genetic anomalies such as mutations and also epigenetic aberrations are responsible for the heterogeneity of this disease. This study identified the 20 most frequently mutated genes reported in PCa based on literature and database survey. Further gene ontology and functional enrichment analysis were conducted to determine their co-modulated molecular and biological pathways. A protein-protein interaction network was used for the identification of hub genes. These hub genes identified were then subjected to survival analysis. The prognostic values of these identified genes were investigated using GEPIA and HPA. Gene Ontology analysis of the identified genes depicted that these genes significantly contributed to the cell cycle, apoptosis, angiogenesis and TGF-beta receptor signalling. Further, the research showed that high expressions of identified mutated genes led to a reduction in the long-term survival of PCa patients, which was supported by immunohistochemical and mRNA expression level data. Our results suggest that identified panel of mutated genes viz., CTNNB1, TP53, ATM, AR and KMT2D play crucial roles in the onset and progression of PCa, thereby providing candidate diagnostic markers for PCa for individualised treatment in the future.