MP61-07 SERUM MICRORNA ANALYSIS: A MINIMALLY INVASIVE ASSAY CORRELATED WITH UPGRADING IN PATIENTS WITH LOW-RISK PROSTATE CANCER

Abstract

INTRODUCTION AND OBJECTIVES: Pathologic upgrading from biopsy to prostatectomy occurs in approximately 30% of prostate cancer cases. PSA, a nonspecific protein, has previously been the primary serum marker for prostate cancer. Markers that more accurately assess risk of aggressiveprostate cancer at the timeof screening are critical for the future management of this disease. The aim of this study was to identify a panel of microRNA (miRNA) from serum that could differentiate patients with low-risk (Gleason 6) prostate cancer on TRUS biopsy specimenswho were either the same grade or upgraded at the time of prostatectomy. METHODS: Total RNA was isolated from serum of patients who had Gleason Sum (GS) 6 prostate cancer at the time of TRUS guided prostate biopsy. These patients were divided into groups with GS 6 that remained GS 6 (same grade) at prostatectomy and those who were upgraded to GS7 (upgrade) at the time of prostatectomy. For the discovery phase, sample pools from each group were profiled via miRNA PCR array (Exiqon). Validation of miRNA expression levels was performed on 29 same and 31 upgrade samples by qRT-PCR. RESULTS: Array analysis of 751miRNA identified34miRNAwith 2-fold differential expression between patients who had Gleason upgrading between biopsies and prostatectomy compared to patients who were same grade. Of these, 20 miRNA were down-regulated and 14 were up-regulated in theupgradedgroup.Additionally, 3miRNAwereexpressed in the upgrade groupwhich were not detected in the same grade group. 17 miRNA were further validated by qRT-PCR on individual samples. miR425-5pandmiR-146-5pwere found tobesignificantlydifferent between the same grade and upgraded groups. ROC curve of logistic regression analysis of theses two showed an area under the curve of 0.691. CONCLUSIONS: Serum samples demonstrated different miRNA expression levels between samples that were same grade or upgraded from Gleason 6 at prostatectomy. This minimally invasive assay could provide an adjunct to PSA and prostate biopsies to better counsel patients on management of low-risk prostate cancer and monitor patients on active surveillance.