MicroRNAs (miRNAs) are small non-coding RNAs that function in regulation of gene expression. Recent studies have also suggested that single nucleotide polymorphisms (SNPs) located in miRNA target sites can influence the prognosis of diverse human cancers, including lung cancer. This study was conducted to evaluate the associations between single nucleotide polymorphisms (SNPs) in miRNA target sites using CLASH data and the survival outcomes of early-stage non-small cell lung cancer (NSCLC) patients.
100 potentially functional polymorphisms were selected based on cancer-related miRNA target site in PolymiRTS database 3.0(http://compbio.uthsc.edu/miRSNP), CLASH data, and CancerGenes database (http://cbio.mskcc.org/cancergenes). All polymorphisms were genotyped using SEQUENOM’s MassARRAY® iPLEX assay according to instructions of the manufacturer. The genotype association with overall survival (OS) and disease-free survival (DFS) in 782 patients with NSCLC who underwent curative surgical resection were analyzed.
Among the 100 SNPs studied, two SNPs showed significant association with survival outcomes. Patients carrying the POLR2A rs2071504TT or CT genotypes showed significantly lower overall survival and disease-free survival than those with the POLR2A rs2071504CC genotype (HR = 1.42, 95% CI = 1.08–1.88, P = 0.01 and HR = 1.34, 95% CI = 1.08–1.67, P = 0.01, respectively). The NR2F6 rs2288539C>T variant was found to be significantly associated with higher overall survival under the recessive model (HR = 0.13, 95% CI = 0.02–0.90, P = 0.04).
Our findings suggest that the POLR2A rs2071504C>T and NR2F6 rs2288539C>T can influence the prognosis of early-stage NSCLC patients.
Clinical trial identification
Legal entity responsible for the study
Jae Yong Park
All authors have declared no conflicts of interest.