Abstract 4010: Prognostic role of miRNAs in resectable non-small cell lung cancer

Abstract

Abstract BACKGROUND MicroRNAs (miRNA) are a class of small RNAs that regulate gene expression, and are implicated in several diseases including cancer. The aim of this study was to analyze the prognostic implications of deregulated miRNAs identified by NGS in a previous study performed on resectable-NSCLC tumor samples. MATERIAL AND METHODS Fresh-frozen tumor and normal adjacent lung tissue samples (N = 195) were obtained by surgical resection from NSCLC patients and storage in RNAlater® at -80°C until analysis. RNA was isolated biological specimens by Trizol based-methods. 22 deregulated miRNA were analyzed in paired tumor/normal samples by RTqPCR using TaqMan® microRNA assays. Statistical analyses were considered significant at p<0.05. RESULTS Patient's median age was 64 years [26-85], 88.2% were male, 66.7% had good performance status (PS = 0), 39.5% were adenocarcinomas and 54.9% presented stage I at the time of the diagnosis. For survival analysis, continuous variables were dichotomized as high (≥ median) and low (< median), using the median expression of each miRNA as a cutoff. Of the 22 miRNAs analyzed only miR-21 and miR-188-5p had prognostic value. We found that patients with high levels of miR-21 and miR-188-5p had a significant reduction in PFS and OS rates. Interestingly, the group of patients with the combined high expression of both miRNAs (miR-21high & miR-188-5phigh) showed shorter PFS and OS (Table 1). Clinico-pathological and analytical variables were included in the multivariate analysis revealing that combined miRNAs is an independent prognostic marker for PFS (HR 0.485 [0.313-0.753]; p = 0.001) and OS (HR 0.389 [0.237-0.638]; p<0.0001]. a P value with Bonferroni correction are shown in parenthesesOSOSPFSPFSMedian (months)PaMedian (months)PamiR-21 (High vs low)42.60 vs 82.600.01622.13 vs 66.970.017miR-188-5p (High vs low)46.67 vs NR0.00524.03 vs 66.970.023Combined miRNAs (miR21 high miR-188 high vs combonations)21.13 vs 83.570.002 (0.008)16.97 vs 56.830.001 (0.004) CONCLUSION Expression of miR-21 and miR-188-5p seems to have a prognostic role in NSCLC, and the combination of both could be an independent prognostic marker in early-stage NSCLC. Table 1. OS and PFS for miR-21 and miR-188-5p in NSCLC patients (univariate analysis) Supported by grants RTICC (RD12/0036/0025 and RD06/0020/1024), TRACE (TRA09-0132) and Beca Roche Oncohematología. Citation Format: Sandra Gallach, Eloisa Jantus-Lewintre, Silvia Calabuig-Fariariñas, Ana Blasco, Ricardo Guijarro, Miguel Martorell, Carlos Camps. Prognostic role of miRNAs in resectable non-small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4010. doi:10.1158/1538-7445.AM2015-4010