Computational strategies for identifying high-risk SNP of PTEN in prostate cancer: A Mutational profiling study

Abstract

The fifth most prevalent cause of cancer-related mortality and the most often diagnosed malignancy in males is prostate cancer. The PTEN tumor suppressor gene is one of the most often altered genomes in prostate cancer. PTEN is a potentially helpful genetic marker to discriminate between indolent and aggressive illness in individuals with clinically localised tumors because loss of PTEN function activates the PI3K-AKT pathway and is highly related with unfavourable oncological outcomes. Moreover, research has suggested that PTEN inactivation due to deletion or mutation influence tumor formation by modifying the immune system and the tumor microenvironment, in addition to its known roles in the PI3K/AKT pathway. Hence, the study aimed to screen all PTEN associated SNPs of prostate cancer for analyzing its structural and functional impact through various computational tools. The results showed C124S and G129R as the most pathogenic variant and are highly conserved causing protein destabilization in prostate cancer. Further, structural analysis through molecular simulation showed that the mutant G129R caused huge instability, high residue fluctuation and loss of compactness in the PTEN protein. The study’s findings shed light on the structural and functional consequences of specific PTEN mutations in prostate cancer.