INTEGRATIVE TISSUE ?OMICS? UNVEIL NOVEL MARKERS AS PREDICTORS OF AGGRESSIVENESS THAT OUTPERFORM GLEASON SCORE IN PROSTATE CANCER

LAGE VICKERS, SOFIA; BIZZOTO, JUAN; VALACCO PIA; SANCHIS, PABLO A; NEMIROVSKY SERGIO; SCORTICATI CARLOS; MAZZA OSVALDO; VAZQUEZ ELBA; COTIGNOLA JAVIER; GUERON GERALDINE

Congreso; Reunión Anual de la Sociedad Argentina de Investigación Clínica 2020; 2020

Prostate cancer (PCa) is the second most frequent cancer and the sixth leadingcause of cancer-related death in men worldwide. Widespread use of prostate-specific antigen (PSA) levels for screening has led to a large increase in theincidence of diagnosed PCa and a reduction in both, the advanced disease and PCamortality rates. However, the overtreatment of PCa is widely recognized. For menwith newly diagnosed PCa, besides from stage, the strongest predictor of lethal PCais the Gleason score (GS). PCa grading has significantly improved since Gleason?soriginal description in the mid-1960s. Literature reflects that, although some prostatecancers (PCas) are histo-pathologically grouped within the same GS, they can differsignificantly in aggressiveness. In this work, we aimed at identifying molecularbiomarkers that could improve risk prediction in PCa. In-depth proteomics analysiswas performed on human PCa and Benign Prostatic Hyperplasia (BPH) tissues. Wethen validated the clinical significance of these peptides through an integrativebioinformatics analysis using public database repositories. We identified highexpression of YWHAZ and NDRG1 to be strongly associated with poor PCaprognosis considering all Gleason scores. YWHAZ and NDRG1 expression definedtwo clearly and distinct subpopulations of patients with high and intermediate risk ofdisease progression. Adjusted multivariable analyses confirmed their independencefrom GS, patient age and TMPRSS2-ERG fusion. Further, ROC analysis unveiledthat YWHAZ outperformed GS beyond 60 months post-diagnosis. We hereby statethe relevance of YWHAZ in PCa, showcasing its role as an independent strongpredictor of aggressiveness, making it a potential prognostic tool when taking intoconsideration the difficulties that PCa presents at the time of decision making.