Genetic polymorphisms in the precursor MicroRNA flanking region and non-small cell lung cancer survival.
BACKGROUND
Previously, we reported that common variants in precursor microRNA (pre-miRNA) sequences played a role in the prediction of non-small cell lung cancer (NSCLC) survival.


OBJECTIVE
To assess whether variants in the pre-miRNA flanking region can influence the clinical behavior of NSCLC.


METHODS
We conducted a two-stage study to examine the impact of a panel of 85 single-nucleotide polymorphisms on the overall survival of 923 patients with NSCLC (568 in the screening set and 355 in the validation set) in China.


RESULTS
Eleven single-nucleotide polymorphisms were primarily associated with NSCLC survival in the univariate analysis. However, in the validation set, only miR-30c-1 rs928508 was consistently an NSCLC survival predictor and the protective role of rs928508 AG/GG genotypes was more pronounced among early-stage (stage I/II) patients and patients treated with surgery. The area under the curve at Year 5 was significantly increased from 0.658 to 0.741 after adding the miR-30c-1 rs928508 risk score to the traditional clinical risk score (stage and surgery). Furthermore, in the genotype-phenotype correlation analysis, rs928508 AG/GG genotypes were associated with a significantly decreased expression of precursor and mature miR-30c (P = 0.009 and 0.011), but not with that of its primary miRNA. The expression of the host nuclear transcription factor Y gene was correlated with pri-mir-30c-1, but not with rs928508 genotypes, implicating the coregulation of the transcription of nuclear transcription factor Y and pri-mir-30c-1.


CONCLUSIONS
Our data indicated, for the first time, that genetic polymorphisms in the pre-miRNA flanking region may be prognostic biomarkers of NSCLC, and rs928508 is such a potential candidate.
Hu
Zhibin
Z
Department of Epidemiology and Biostatistics and Ministry of Education Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, China. zhibin_hu@njmu.edu.cn
Shu
Yongqian
Y
Chen
Yijiang
Y
Chen
Jiaping
J
Dong
Jing
J
Liu
Yao
Y
Pan
Shiyang
S
Xu
Lin
L
Xu
Jing
J
Wang
Yi
Y
Dai
Juncheng
J
Ma
Hongxia
H
Jin
Guangfu
G
Shen
Hongbing
H
D019540:Area Under Curve; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D035683:MicroRNAs