Abstract 1475: Plasma circulating miRNAs: a new potential biomarker for prostate cancer diagnosis

Abstract

Abstract MicroRNAs (miRNAs) are a class of small, non-coding, single-stranded RNAs that negatively regulate gene expression mainly binding to 3′-untranslated region (UTR) of target mRNAs at the post-transcriptional level. Recent studies have demonstrated that aberrant expressions of miRNAs are closely associated with the development, invasion, metastasis and prognosis of various cancers including prostate cancer (PCa). However, while the majority of miRNAs are found at the intracellular level, a significant number of miRNAs have been observed outside the cells, including various body fluids. Circulating miRNAs act as ‘extracellular communication RNAs’ that could be particularly relevant in the context of neoplastic diseases and may be useful for early diagnosis as well as to predict the clinical outcome and the treatment response. The aim of this study was to investigate the hypothesis that changes in circulating miRNAs represent potentially useful minimally invasive biomarkers for the diagnosis, staging and prediction of outcome in prostate cancer. From 2012 onwards, consecutive men undergoing 12-core prostate biopsy at Sant’Andrea Hospital of Rome were enrolled into a prospective database. Indications for a prostatic biopsy were a PSA value ≥ 4 ng/ml and/or a positive digital rectal examination (DRE). We selected, as a training set, 32 patients with a mean age and PSA of 66.6 years (SD ±7.9) and 14.3 (range to 0,53-185) ng/ml, respectively. Among them 16 patients (50%) have cancer on biopsy; 8 with Gleason score 6; 3 with a Gleason score 7 and 5 with a Gleason score ≥8 and 16 patients (50%) are control individuals with non-neoplastic prostate disease (i.e. prostatitis). Profiling of microRNAs by deep sequencing allowed us to identify a “signature” of 27 microRNAs aberrant expressed in prostate cancer samples. Receiver-operator characteristics (ROC) curve analysis was used to evaluate the diagnostic accuracy of miRNAs for the final histopathological diagnosis of prostate cancer. An AUC of 0.77; 95%CI was observed for the diagnosis of prostate cancer using all 27 microRNAs, which is correlated with the Gleason score of the analyzed samples, while results to be independent from the respective values of serum PSA. Moreover, ROC curve analysis also highlighted a small subgroup consisting of 6 miRNAs with a high predictive power able to discriminate patients with prostate cancer (AUC = 0.805; 95%CI). This signature is under validation in an indipendent cohort of patients. These preliminary observations suggest that circulating miRNAs could represent promising biomarkers for non-invasive diagnosis in prostate cancer unrelated to PSA. Citation Format: Simona Giglio, Cosimo De Nunzio, Roberto Cirombella, Stefano Volinia, Emidio Luciani, Andrea Tubaro, Andrea Vecchione. Plasma circulating miRNAs: a new potential biomarker for prostate cancer diagnosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1475. doi:10.1158/1538-7445.AM2014-1475