A Genetic Polymorphism in pre-miR-27a Confers Clinical Outcome of Non-Small Cell Lung Cancer in a Chinese Population

• Published in: PloS one Vol. 8; no. 11; p. e79135
• Main Authors: Xu, Jiali, Yin, Zhiqiang, Shen, Hong, Gao, Wen, Qian, Yingying, Pei, Dong, Liu, Lingxiang, Shu, Yongqian
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.11.2013; Public Library of Science (PLoS)
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Asian Continental Ancestry Group - genetics; Biomarkers; Breast cancer; Cancer; Carboplatin - administration & dosage; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - ethnology; Carcinoma, Non-Small-Cell Lung - genetics; Chemotherapy; China; Cisplatin - administration & dosage; Clinical outcomes; Deregulation; Diabetes; Female; Gastric cancer; Gene expression; Gene Frequency; Gene polymorphism; Gene regulation; Genes; Genetic aspects; Genotype; Genotypes; Genotyping; Humans; Identification methods; Kaplan-Meier Estimate; Kinases; Logistic Models; Lung cancer; Lung diseases; Lung Neoplasms - drug therapy; Lung Neoplasms - ethnology; Lung Neoplasms - genetics; Male; Medical prognosis; Medical research; MicroRNA; MicroRNAs; MicroRNAs - genetics; Middle Aged; miRNA; Multivariate Analysis; Non-small cell lung cancer; Non-small cell lung carcinoma; Oncology; Outcome Assessment (Health Care) - statistics & numerical data; Patient outcomes; Patients; Platinum; Polymorphism; Polymorphism, Single Nucleotide; Population; Prognosis; Proportional Hazards Models; Proteins; Regression analysis; RNA Precursors - genetics; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Small cell lung cancer; Stomach cancer; Subgroups; Suppressors; Survival; Transcription; Transcription (Genetics); Vascular endothelial growth factor; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0079135

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. 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. 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. 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.