Prognostic value and functional characterization of miR-141 and miR-200c expression levels in resected NSCL

Introduction: Several treatments in non-small cell lung cancer (NSCLC) are histology-dependent, and the need for histology-related markers is increasing. We have examined the prognostic value of the miR-200 family in overall survival (OS) of early-stage NSCLC patients with adenocarcinoma or squamous cell carcinoma (SCC). Experimental design: The expression of all five members of the miR-200 family was determined using TaqMan assays in 155 tumors from resected NSCLC patients. Functional characterization studies were conducted in the H23 lung cancer cell line. Results: High miR-200c expression was associated with shorter OS in the entire cohort ( P = 0.024). High miR-200c ( P = 0.0004) or miR-141 ( P = 0.009) expression correlated with shorter OS in adenocarcinoma – but not in SCC. In the multivariate analysis, the miR-141/200c score emerged as an independent prognostic factor for OS in the entire cohort (OR, 2.787; P = 0.033) and in adenocarcinoma patients (OR, 10.649; P = 0.002) but not in SCC patients. Functional analyses showed that miR-200c, but not miR-141, was related to mesenchymal-epithelial transition (MET) and affected cell migration and E-cadherin levels, while overexpression of miR-141 was associated with higher levels of VEGF in vitro ( P = 0.04) and with higher blood microvessel density in patient tumor samples ( P < 0.001). Conclusions: High miR-141 and miR-200c expression are associated with poorer outcome in NSCLC patients with adenocarcinoma but not in those with SCC. miR-141 seems to act through angiogenesis, while miR-200c may play a role in the regulation of MET. FIS 12/405, SEPAR, SOCAP, FUCAP.