Serum microRNA-365 in combination with its target gene TTF-1 as a non-invasive prognostic marker for non-small cell lung cancer

Background: MicroRNA (miR)-365 functions as a tumor suppressor in non-small cell lung cancer (NSCLC) cells by targeting thyroid transcription factor 1 (TTF-1). Aim: To investigate miR-365 and TTF-1 mRNA expression in serum of NSCLC and their associations with patients' prognosis. Methods: MiR-365 and TTF-1 mRNA expression in 100 NSCLCs and 100 healthy control sera were detected by quantitative real-time PCR (qRT-PCR). Results: MiR-365 expression level was significantly lower in NSCLC serum samples than in healthy control serum samples (P < 0.001), while TTF-1 mRNA expression level was significantly increased in NSCLC serum samples compared to healthy control serum samples (P < 0.001). In addition, low miR-365 expression and high TTF-1 expression, alone or in combination, were all significantly associated with poor differentiation (P = 0.008, 0.008 and 0.001, respectively), advanced TNM stage (P = 0.001, 0.005 and < 0.001 respectively) and positive lymph node metastasis (P = 0.02, 0.02 and 0.01, respectively) of NSCLC patients. Notably, NSCLC patients with combined low miR-365 expression and high TTF-1 expression (miR-365-low/TTF-1-high) had shortest overall survival (P < 0.001). Furthermore, multivariate analysis showed that miR-365 expression (P = 0.01), TTF-1 expression (P = 0.01), and combined expression of miR-365 and TTF-1 (miR-365/TTF-1, P = 0.001) were all independent prognostic factors for overall survival in NSCLC patients. Conclusions: Our data reveal that preoperative serum miR-365 and TTF-1 mRNA levels may be both effective indicators of tumor aggressiveness in human NSCLC. More interestingly, miR-365 and its target gene TTF-1 appear to be synergistic risk factors for the reduction in overall survival of patients with NSCLC. (C) 2015 Elsevier Masson SAS. All rights reserved.