Genetic polymorphisms in the precursor MicroRNA flanking region and non-small cell lung cancer survival. Am J Respir Crit Care Med 2011 Mar 01;183(5):641-8
Date
10/05/2010Pubmed ID
20889907DOI
10.1164/rccm.201005-0717OCScopus ID
2-s2.0-79952233124 (requires institutional sign-in at Scopus site) 52 CitationsAbstract
RATIONALE: 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.
OBJECTIVES: 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.
MEASUREMENTS AND MAIN 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.
Author List
Hu Z, Shu Y, Chen Y, Chen J, Dong J, Liu Y, Pan S, Xu L, Xu J, Wang Y, Dai J, Ma H, Jin G, Shen HAuthor
Jing Dong PhD Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Area Under CurveCarcinoma, Non-Small-Cell Lung
Female
Humans
Kaplan-Meier Estimate
Lung Neoplasms
Male
MicroRNAs
Middle Aged
Pilot Projects
Polymorphism, Single Nucleotide
Reverse Transcriptase Polymerase Chain Reaction
