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).


OBJECTIVE
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.
Department of Respiratory Medicine, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471009, Henan Province, China.
Yanyan
Y
Liu
First Affiliated Hospital to Henan University of Science and Technology, Luoyang 471009, Henan Province, China.
Guoxiu
G
Zhang
Department of Respiratory Medicine, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471009, Henan Province, China.
Haiyan
H
Li
Department of Respiratory Medicine, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471009, Henan Province, China.
Lihong
L
Han
Department of Respiratory Medicine, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471009, Henan Province, China.
Aiguo
A
Fu
Department of Respiratory Medicine, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471009, Henan Province, China.
Nali
N
Zhang
Department of Respiratory Medicine, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471009, Henan Province, China. Electronic address: youg_zheng@163.com.
Youguang
Y
Zheng
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D016022:Case-Control Studies; D002454:Cell Differentiation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000097:blood* / Q000235:genetics; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000097:blood* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D000074482:Thyroid Nuclear Factor 1; D013997:Time Factors; D014157:Transcription Factors / Q000097:blood* / Q000235:genetics
D014408:Biomarkers, Tumor; C546819:MIRN365 microRNA, human; D035683:MicroRNAs; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors
MicroRNA-365; Non-small cell lung cancer; Prognosis; Quantitative real-time PCR; Thyroid transcription factor 1