Urine Extracellular Vesicle GATA2 mRNA Discriminates Biopsy Result in Men with Suspicion of Prostate Cancer.

PURPOSE: PSA has limited performance in detecting prostate cancer (PCa). The transcription factor GATA2 is expressed in aggressive PCa. Here we analyzed the predictive value of urine extracellular vesicle (EV) GATA2 mRNA alone and in combination with a multigene panel to improve detection of PCa and high-risk disease. MATERIALS AND METHODS: GATA2 mRNA was analyzed in matched EVs isolated from urines pre- and post-prostatectomy (n=16) and paired urine and tissue prostatectomy samples (n=19). EV GATA2 mRNA performance to distinguish PCa and high-grade disease was tested in training (n=52) and validation (n=165) cohorts. The predictive value of a multigene score including GATA2, PCA3 and TMPRSS2-ERG (GAPT-E) was tested in both cohorts. RESULTS: Confirming its prostate origin, urine EV GATA2 mRNA levels significantly dropped after prostatectomy and correlated with PCa tissue GATA2 mRNA levels. In the training and validation cohort, GATA2 discriminated PCa (area under the curve (AUC), 0.74 and 0.66) and high-grade disease (AUC 0.78 and 0.65), respectively. Notably, the GAPT-E score improved discrimination of PCa (AUC 0.84 and 0.72) and high-grade cancer (AUC 0.85 and 0.71), in both cohorts when compared with each biomarker alone and PT-E (PCA3 and TMPRSS2-ERG). A GAPT-E score for high-grade PCa would avoid 92.1% of unnecessary prostate biopsies, compared to 61.9% when a PT-E score is used. CONCLUSIONS: Urine EV GATA2 mRNA analysis improves the detection of high-risk PCa and may reduce the number of unnecessary biopsies.