What Is The Role Of Microrna-301a Expression As A Diagnostic And Predictive Marker Of Biochemical Recurrence For Prostate Cancer?

19 Background: Prostate specific antigen (PSA) screening for prostate cancer (PCa) remains controversial, due to its association with an increase in overdiagnosis of clinically insignificant PCa, and overtreatment. Hence, the need for more specific biomarkers to detect PCa and determine its prognosis. MicroRNA expression has previously been demonstrated as a biomarker to detect several malignancies. Studies suggest that microRNA-301a (miR-301a) inhibits the pro-apoptotic function of RUNX3, a transcription factor, and consequently activates ROCK1-mediated survival signaling in PCa. This study establishes the role of miR-301a as a reliable biomarker that can distinguish between patients with benign prostate hyperplasia (BPH) and PCa, and predict biochemical recurrence (BCR) after definitive treatment of PCa. Methods: Serum samples and tissue from prostate biopsies were collected from patients with an elevated PSA prospectively. The expression of miR- 301a was measured via reverse transcriptase-polymerase chain reaction. Additionally, miR-301a expression was retrospectively evaluated in prostatic tissue of 50 patients with PCa, including benign tissue, and correlated with clinico-pathological characteristics to predict BCR. Immunohistochemistry was performed to confirm the molecular target of miR-301a in cancerous tissue. Results: miR-301a demonstrated a significantly higher expression (p = 0.013) in both PCa tissue (Gleason 6 & 7 PCa) and serum samples (p = 0.011) when compared to BPH. Expression of miR-301a in Gleason 6 & 7 prostatectomy specimens positively correlated with patients who developed BCR when compared to patients who did not. When compared to the current nomogram for the prediction of PCa (i.e., PSA, age, race, Gleason score, and family history), incorporation of miR-301a was associated with a superior prediction of BCR at three years post-prostatectomy. Conclusions: miR-301a expression is a valuable tool for diagnosing PCa in patients with an elevated PSA. Combining miR-301a with PSA is associated with better risk stratification of PCa patients, and may help facilitate clinical decision making.