INTEGRATIVE TISSUE PROTEOMICS DISSECTS CLEAR AND DISTINCT PROTEOMES IN PROSTATE CANCER AIDING IN THE DISCOVERY OF NOVEL RISK STRATIFICATION BIOMARKERS.

BIZZOTTO JUAN; ALEJANDRA PAEZ; ELBA VAZQUEZ; VALACCO PIA; OSVALDO MAZZA; GERALDINE GUERON; LAGE VICKERS, SOFIA; NEMIROVSKY SERGIO; COTIGNOLA JAVIER

Mar del Plata

Congreso; Sociedad Argentina de Investigacion Clinica; 2018

SAIC

Formalin-fixed, paraffin-embedded (FFPE) tissues are highly valuable resources for translational proteomics studies. Although it is well known that prostate cancer (PCa) is a progressive disease involving multiple gene alterations, little is known at the proteome level. The biopsy Gleason score (BGS) is used as an aid for physicians to evaluate the prognosis of men with PCa using samples from prostate tissues. However, BGS can fail to clearly distinguish between some Gleason grades, leading to incorrect treatment of PCa patients. To identify potential PCa protein biomarkers for risk stratification, we carried out an in-depth proteomics analysis (ESI-MS/MS) using human PCa and Benign Prostatic Hyperplasia (BPH) FFPE tissues. We have explored the high-throughput data in two different ways.First, we identified differentially expressed proteins between PCa and BPH samples. We filtered the proteins based on spectral counts, resulting in the selection of 11 candidates. To assess the clinical significance of these peptides we performed an integrative bioinformatics analysis using public database repositories (Oncomine, cBioportal, TCGA, GEO, 29 datasets, n=3794). We identified YWHAZ, a novel androgen receptor (AR) co-activator, to be strongly associated with poor prognosis across different PCa datasets. Overall and relapse-free survival were significant shorter when comparing patients with high vs. low expression for this gene (Hazard Ratio >1, P