A genetic polymorphism in pre-miR-27a confers clinical outcome of non-small cell lung cancer in a Chinese population.
BACKGROUND
Recent evidence indicates that microRNAs (miRNAs) can function as tumor suppressors and oncogenes. Single nucleotide polymorphisms (SNPs) at miRNA genes can influence the maturation of miRNAs or miRNA-mediated transcriptional regulation. Our objective was to investigate the association of SNPs in deregulated miRNAs with clinical outcome in patients with non-small cell lung cancer (NSCLC) in a Chinese population.


METHODS
Deregulated miRNAs in NSCLC and their SNPs were identified through public databases. A single SNP, rs895819 in pre-miR-27a, was found suitable for selection. TaqMan assays were performed for genotyping and to assess the effect on the overall survival (OS) and chemotherapy response in 576 NSCLC patients.


RESULTS
Log-rank test and Cox regression analysis indicated that the G allele of rs895819 was associated with shorter survival and increased risk of death in NSCLC [dominant model: 22.0 vs. 46.0 months, P<0.001; adjusted hazard ratio (HR) = 1.71, 95% confidential interval (CI): 1.12-2.26]. Further stepwise regression analysis suggested that this SNP was an independently unfavorable factor for the prognosis of NSCLC and the effect remained significant in subgroup analysis stratified by clinical parameters and treatment status. Moreover, multivariate logistic regression analysis showed that the subjects with AG/GG genotypes of rs895819 had significantly decreased response rate to platinum-based chemotherapy compared to those with the AA genotype.


CONCLUSIONS
Our results suggest that the pre-miR-27a rs895819 polymorphism may influence NSCLC patients' clinical outcome. Further large sample studies should be used to validate our findings.
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Jiali
J
Xu
Zhiqiang
Z
Yin
Hong
H
Shen
Wen
W
Gao
Yingying
Y
Qian
Dong
D
Pei
Lingxiang
L
Liu
Yongqian
Y
Shu
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D002681:China; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008175:Lung Neoplasms / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D012322:RNA Precursors / Q000235:genetics
C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D012322:RNA Precursors; D016190:Carboplatin; D002945:Cisplatin