185P - Association of polymorphisms in the microRNA target sites and survival of patients in early-stage non-small-cell lung cancer

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Non-Small-Cell Lung Cancer, Early Stage
Translational Research
Presenter Shin Yup Lee
Citation Annals of Oncology (2014) 25 (suppl_4): iv58-iv84. 10.1093/annonc/mdu326
Authors S.Y. Lee1, J.E. Choi1, H.S. Jeon1, M.J. Hong1, Y.Y. Choi1, S.S. Yoo1, E.B. Lee1, W.K. Lee2, Y.T. Kim3, S. Jheon3, J.W. Son4, J.Y. Park1
  • 1Lung Cancer Center, Kyungpook National University Medical Center, 702-210 - Daegu/KR
  • 2Biostatistics Center, Kyungpook National University Medical School, Daegu/KR
  • 3Department Of Thoracic And Cardiovascular Surgery, Seoul National University College of Medicine, Seoul/KR
  • 4Department Of Internal Medicine, Konyang University Hospital, Daejeon/KR

Abstract

Aim

MicroRNAs (miRNAs) have a key role in carcinogenesis through the negatve regulation of their target genes. Therefore, genetic variations in miRNAs or miRNA target sites may affect miRNA-mRNA interactions, thereby result in altered expression of target genes. This study was conducted to investigate the associations between single nucleotide polymorphisms (SNPs) located in the miRNA target sites (poly-miRTSs) and survival of patients with early-stage non-small cell lung cancer (NSCLC).

Methods

Using public SNP database and miRNA target sites prediction program, 354 poly-miRTSs were selected for genotyping. Among these, only 154 SNPs could be applied to Sequenom's MassARRAY platform and investigated in 357 patients. A replication study was performed on an independent patient population (n = 479). Renilla luciferase assay and reverse transcription-PCR were conducted to examine functional relevance of potentially functional poly-miRTSs.

Results

Of the 154 SNPs analyzed in the discovery set, 14 SNPs were significantly associated with survival outcomes. Among these, KRT81 rs3660C > G was found to be associated with survival outcomes in the validation cohort. In combined analysis, patients with the rs3660 GC + CC genotype had a significantly better overall survival (OS) compared with those with GG genotype (adjusted hazard ratio for OS, 0.65; 95% confidence interval 0.50-0.85; p = 0.001). An increased expression of the reporter gene for the C allele of rs3660 compared with the G allele was observed by luciferase assay. Relative expression level of KRT81 in tumor tissues was significantly higher in CC genotype compared with GG or GC genotypes.

Conclusions

The rs3660G > C affects KRT81 expression and thus influences survival in early-stage NSCLC. The analysis of the rs3660G > C polymorphism may be useful to identify patients at high risk of a poor disease outcome.

Disclosure

All authors have declared no conflicts of interest.