217PMICRORNA-89 EXPRESSION AS A PROMISING PROGNOSTIC BIOMARKER FOR ADVANCED COLORECTAL CANCER

ABSTRACT Aim: Colorectal cancer (CRC) is the third most common cancer and is a leading cause of cancer-related deaths worldwide. Colorectal cancer arises by sequential accumulation of genetic and epigenetic alterations. Recently, microRNAs (miRNAs) have emerged as key players in tumor progression in various cancers, and their expression alterations are being considered as the basis for development of important diagnostic/predictive/prognostic biomarkers. We aimed to evaluate the potential of miRNAs as prognostic biomarker for advanced CRC. Methods: MiRNA microarrays profiling was performed in CRC specimens derived from tumors with specific genotypes, including mutations in the KRAS & BRAF genes, and their microsatellite instability [MSI] status. The microarray profiling analysis revealed that miR-89 was specifically upregulated in CRCs with BRAF mutation without MSI, and reflected poor prognosis in these patients. Therefore, we focused on miR-89 and analyzed its expression levels in a cohort of 67 stage IV CRCs (TNM staging system by UICC 7th). miR-89 expression analysis was performed by quantitative reverse transcription PCR using a comparative Ct method, and its expression status was correlated with various clinico-pathological factors. Patient survival analysis were performed by Cox proportional hazards model and Kaplan-Meier analysis. Results: Of 67 patients with stage IV CRCs, 15 patients showed KRAS mutations, while 4 patients had BRAF mutations. None of the 67 patients had MSI. The mean expression levels of miR-89 was 141.82 (range: 0.003778-6330.531), and the median value was 3.45. Therefore, we determined the cut-off value and tumors with miR-89 expression levels more than 4.0 were categorized as “high miR-89” group. High miR-89 expression (n = 33) correlated with poor mortality (univariate hazards ratio = 2.124, 95% confidence interval: 0.23 - 0.95, P = 0.03) and with poor median survival time (MST) of 20.1 months (MST of the low miR-89 expression group [n = 34] was 38.3 months, P = 0.03 ) Conclusions: Our data indicate that miR-89 is a promising prognostic biomarker for advanced CRC. We believe that performing the functional analysis using miR-89 or its inhibitors may lead to the development novel treatment options for patients with advanced CRC in future. Disclosure: All authors have declared no conflicts of interest.