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Am J Respir Crit Care Med. 2011 Mar 1;183(5):641-8. doi: 10.1164/rccm.201005-0717OC. Epub 2010 Oct 1.

Genetic polymorphisms in the precursor MicroRNA flanking region and non-small cell lung cancer survival.

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  • 1Department 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

Abstract

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.

PMID:
20889907
[PubMed - indexed for MEDLINE]
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