MP47-01 OVEREXPRESSED MIR-27A-3P IS AS INDEPENDENT PROGNOSTIC FACTOR FOR RECURRENCE IN CLEAR CELL RENAL CELL CARCINOMA

INTRODUCTION AND OBJECTIVES: MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression and influence tumor development and progression. We previously identified miRNAs upregulated in clear cell renal cell carcinoma (ccRCC) compared to matched-pair normal kidney using microarray analysis. However, such cancer-specific miRNAs are not always associated with patient survival and/or recurrence. This study aims to identify miRNAs that are upregulated in ccRCC and that are also associated with survival and/or recurrence. METHODS: We obtained 183 ccRCC clinical specimens from patients who underwent nephrectomy at our hospital between 2000 and 2012. We selected 24 frozen samples, of which 11 patients had evidence of disease or died from cancer (Group 1) and 13 patients had no evidence of disease (Group 2) within two years after surgery. Quantitative real time PCR (qRT-PCR) was performed on the samples to expression of 22 miRNAs that our microarray results indicated as upregulated in ccRCC, and hits were further validated using another 159 frozen samples. Functional analysis of the miRNA was performed using siRNA-mediated knockdown in RCC cell lines. RESULTS: Five miRNAs (Table.1) were upregulated in Group 1 compared to Group 2, and we validated these results using 159 samples of ccRCC. High miR-21-3p (p <0.01) and miR-193b-5p (p <0.05) levels correlated with worse cancer-specific survival. In ccRCC patients without metastasis at time of diagnosis (n1⁄4140), high miR-27a-3p (p <0.01) levels correlated with worse progression-free survival. Multivariate analysis showed that miR27a-3p was an independent prognostic factor for recurrence (Table.2). Knockdown of miR-27a-3p by siRNA suppressed cell proliferation, migration, invasion and colony formation in RCC cell lines. CONCLUSIONS: These results suggest that miR-27a-3p is a good prognostic biomarker to predict recurrence independent of clinicpathological characteristics and could function as an oncomir in ccRCC. As such, miR-27a-3p may be a candidate for targeted molecular therapy. Source of Funding: none