Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer.
OBJECTIVE
Recent findings that human serum contains stably expressed microRNA (miRNA) have revealed a great potential of serum miRNA signature as disease fingerprints to predict survival. We used genome-wide serum miRNA expression analysis to investigate the role of serum miRNA in predicting prognosis of non-small-cell lung cancer (NSCLC).


METHODS
To control disease heterogeneity, we used patients with stages I to IIIa lung adenocarcinoma and squamous cell carcinoma, who were treated with both operation and adjuvant chemotherapies. In the discovery stage, Solexa sequencing followed by individual quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays was used to test the difference in levels of serum miRNAs between 30 patients with longer survival (alive and mean survival time, 49.54 months) and 30 patients with shorter survival matched by age, sex, and stage (dead and mean survival time, 9.54 months). The detected serum miRNAs then were validated in 243 patients (randomly classified into two subgroups: n = 120 for the training set, and n = 123 for the testing set).


RESULTS
Eleven serum miRNAs were found to be altered more than five-fold by Solexa sequencing between longer-survival and shorter-survival groups, and levels of four miRNAs (ie, miR-486, miR-30d, miR-1 and miR-499) were significantly associated with overall survival. The four-miRNA signature also was consistently an independent predictor of overall survival for both training and testing samples.


CONCLUSIONS
The four-miRNA signature from the serum may serve as a noninvasive predictor for the overall survival of NSCLC.
Hu
Zhibin
Z
Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, 140 Hanzhong Rd, Nanjing 210029, China.
Chen
Xi
X
Zhao
Yang
Y
Tian
Tian
T
Jin
Guangfu
G
Shu
Yongqian
Y
Chen
Yijiang
Y
Xu
Lin
L
Zen
Ke
K
Zhang
Chenyu
C
Shen
Hongbing
H
D000230:Adenocarcinoma / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D012306:Risk
D035683:MicroRNAs