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

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

Virtual

Congreso; LXV Reunión anual de la Sociedad Argentina de Investigación Clínica; 2020

Sociedad Argentina de Investigación Clínica

Prostate cancer (PCa) is the second most frequent cancer and thesixth leading cause of cancer-related death in men worldwide. Wide-spread use of prostate-specific antigen (PSA) levels for screeninghas led to a large increase in the incidence of diagnosed PCa anda reduction in both, the advanced disease and PCa mortality rates.However, the overtreatment of PCa is widely recognized. For menwith newly diagnosed PCa, besides from stage, the strongest pre-dictor of lethal PCa is the Gleason score (GS). PCa grading hassignificantly improved since Gleason?s original description in themid-1960s. Literature reflects that, although some prostate cancers(PCas) are histo-pathologically grouped within the same GS, theycan differ significantly in aggressiveness. In this work, we aimed atidentifying molecular biomarkers that could improve risk predictionin PCa. In-depth proteomics analysis was performed on humanPCa and Benign Prostatic Hyperplasia (BPH) tissues. We then val-idated the clinical significance of these peptides through an inte-grative bioinformatics analysis using public database repositories.We identified high expression of YWHAZ and NDRG1 to be stronglyassociated with poor PCa prognosis considering all Gleason scores.YWHAZ and NDRG1 expression defined two clearly and distinctsubpopulations of patients with high and intermediate risk of dis-ease progression. Adjusted multivariable analyses confirmed theirindependence from GS, patient age and TMPRSS2-ERG fusion.Further, ROC analysis unveiled that YWHAZ outperformed GS be-yond 60 months post-diagnosis. We hereby state the relevance ofYWHAZ in PCa, showcasing its role as an independent strong pre-dictor of aggressiveness, making it a potential prognostic tool whentaking into consideration the difficulties that PCa presents at the timeof decision making.