Human Prostate and Benign Prostate Hyperplasia, LC MSMS

It is well known that prostate cancer (PCa) is a progressive disease involving multiple gene alterations. The Gleason score (GS) is a morphologic feature of PCa used in the clinic to evaluate the risk of disease progression. However, GS often fail to clearly distinguish between indolent and aggressive disease. The aim of this study was to identify potential biomarkers for PCa risk stratification. An in-depth proteomics analysis (LC ESI-MS/MS) was performed on human PCa and BPH tissues. First, we identified differentially expressed proteins between PCa and BPH samples. We then filtered the proteins based on peptide spectrum matches and selected a panel of candidates. To assess and validate the clinical significance of these peptides we performed an integrative bioinformatics analysis using public database repositories. We identified YWHAZ, an androgen receptor downstream target, as one of the proteins enriched in PCa compared with BPH. We also found a strong association of YWHAZ expression with poor prognosis across different PCa datasets. Briefly, overall and relapse-free survival were significantly shorter in PCa cases expressing high vs. low YWHAZ expression. Further, multivariate analyses displayed high significant correlation with poor prognosis, independent from GS, age, PSA at diagnosis and TMPRSS2-ERG fusion. A multi-cancer screening for YWHAZ unveils amplification as the main alteration for this gene correlating with increased mRNA expression levels across all types of cancer through the cBioPortal platform. YWHAZ rises as a promising prognostic factor in PCa, independent from GS, aiding in disease risk stratification.