Decreased expression of miR-204 in plasma is associated with a poor prognosis in patients with non-small cell lung cancer.
In order to identify novel non-invasive biomarkers with high accuracy for the screening of non-small cell lung cancer (NSCLC), we investigated the predictive power of 4 microRNAs (miR-146, miR-204, miR-106a and miR-124) in plasma samples obtained from patients with NSCLC and healthy controls (n=50; training phase) by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We found that the levels of miR-204 in the patients with NSCLC were significantly dysregulated compared with the healthy controls, and thus this miRNA was selected for further validation. For the validation phase, RT-qPCR was performed on plasma samples from patients with NSCLC and healthy controls (n=176) in order to examine the expression levels of the candidate miRNA, miR-204. The results revealed that the plasma levels of miR-204 were significantly downregulated in the patients with NSCLC compared with the healthy controls (p<0.001). The value of the area under the receiver operating characteristic (ROC) curve obtained for miR-204 was 0.809 (sensitivity, 76%; specificity, 82%), which was higher than the values obtained for carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). The expression of miR-204 in plasma significantly correlated with the tumor stage (p=0.009) and distant metastasis (p=0.048). A log-rank test revealed that lower plasma levels of miR-204 were associated with a shorter overall survival and disease-free survival (p=0.006 and 0.0065, respectively). Both univariate and multivariate Cox regression analyses indicated that a lower miR-204 expression level in plasma was a prognostic factor with a relative risk of death of 1.936 and 1.712, respectively. On the whole, our results suggest that the decreased expression of miR-204 in plasma is a promising biomarker for the detection of NSCLC and the prediction of poor survival in patients with the disease.
Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai 200032, P.R. China.
Weigang
W
Guo
Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai 200032, P.R. China.
Yongxing
Y
Zhang
Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai 200032, P.R. China.
Yi
Y
Zhang
Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai 200032, P.R. China.
Yu
Y
Shi
Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai 200032, P.R. China.
Junjie
J
Xi
Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai 200032, P.R. China.
Hong
H
Fan
Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai 200032, P.R. China.
Songtao
S
Xu
D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D018395:CA-19-9 Antigen / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000706:statistics & numerical data
D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen; C549404:MIRN204 microRNA, human; D035683:MicroRNAs