Serum microRNA 125b as a diagnostic or prognostic biomarker for advanced NSCLC patients receiving cisplatin-based chemotherapy

摘要

Aim: To investigate the expression profile of microRNAs in inoperable advanced non-small cell lung cancer (NSCLC) patients receiving chemotherapy and the potential relevance of microRNAs to clinicopathological characteristics and prognosis.Methods: Serum samples were taken from 260 inoperable advanced NSCLC patients and 260 healthy individuals.All the patients received cisplatin-based chemotherapy,including NP/NC regimens,GP/GC regimens,and TP/TC regimens.The serum levels of microRNAs (miR-125b,miR-10b,miR-34a and miR-155) were determined by quantitative real-time PCR.Results: Serum levels of the 4 microRNAs examined in NSCLC patients were significantly increased as compared with healthy individuals.The levels of miR-125b and miR-155 were changed in a similar pattern: the patients with stage Ⅳ disease had the highest one,while the patients with stage Ⅲ A and stage Ⅲ B disease showed similar increased levels.The levels of miR-10b and miR-34a in the patients with different stages were increased to similar extent.The level of miR-125b in poorly differentiated cancer was significantly higher than those in well and moderately differentiated cancers,while the levels of miR-10b,miR-34a,and miR-155 did not significantly differ with cancer differentiation.Among the 4 microRNAs examined,only miR-125b was significantly associated with therapeutic response,exhibiting higher expression levels in non-responsive patients.Furthermore,the high level of miR-125b was significantly correlated with poor patient survival.A multivariate Cox regression analysis showed that the expression level of miR-125b was an independent prognostic marker in NSCLC patients.Conclusion: Our results suggest that miR-125b is a potential diagnostic or prognostic biomarker for NSCLC.This finding has important implications for development of targeted therapeutics to overcome chemotherapeutic resistance in NSCLC.