Comparative Proteome Profiling and Mutant Protein Identification in Metastatic Prostate Cancer Cells by Quantitative Mass Spectrometry-based Proteogenomics.

Abstract

Prostate cancer (PCa) is the most frequent cancer found in males worldwide. The aim of this study was to identify new biomarkers using mutated peptides for the prognosis and prediction of advanced PCa, based on proteogenomics. The tryptic peptides were analyzed by tandem mass tag-based quantitative proteomics. Proteogenomics were used to identify mutant peptides as novel biomarkers in advanced PCa. Using a human database, increased levels of INTS7 and decreased levels of SH3BGRL were found to be associated with the aggressiveness of PCa. Using proteogenomics and a cancer mutation database, 70 mutant peptides were identified in PCa cell lines. Using parallel reaction monitoring, the expression of seven mutant peptides was found to be altered in tumors, amongst which CAPN2 D22E was the most significantly up-regulated mutant peptide in PCa tissues. Altered mutant peptides present in PCa tissue could be used as new biomarkers in advanced PCa.