Yanyan Liu1, Guoxiu Zhang2, Haiyan Li1, Lihong Han1, Aiguo Fu1, Nali Zhang1, Youguang Zheng3. 1. Department of Respiratory Medicine, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471009, Henan Province, China. 2. First Affiliated Hospital to Henan University of Science and Technology, Luoyang 471009, Henan Province, China. 3. Department of Respiratory Medicine, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471009, Henan Province, China. Electronic address: youg_zheng@163.com.
Abstract
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.
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 NSCLCpatients. Notably, NSCLCpatients 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 NSCLCpatients. CONCLUSIONS: Our data reveal that preoperative serum miR-365 and TTF-1 mRNA levels may be both effective indicators of tumor aggressiveness in humanNSCLC. 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.
Authors: Javaid Ahmad Wani; Sabhiya Majid; Zuha Imtiyaz; Muneeb U Rehman; Rana M Alsaffar; Naveed Nazir Shah; Sultan Alshehri; Mohammed M Ghoneim; Syed Sarim Imam Journal: Diagnostics (Basel) Date: 2022-07-01