title: Genetic polymorphisms in the precursor MicroRNA flanking region and non-small cell lung cancer survival.
abstract: 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.
authors.affiliation: 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
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Shu
authors.forename: Yijiang
authors.initials: Y
authors.lastname: Chen
authors.forename: Jiaping
authors.initials: J
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.forename: Yao
authors.initials: Y
authors.lastname: Liu
authors.forename: Shiyang
authors.initials: S
authors.lastname: Pan
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
mesh_terms: 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
chemical_list: D035683:MicroRNAs