A Genetic Polymorphism in pre-miR-27a Confers Clinical Outcome of Non-Small Cell Lung Cancer in a Chinese Population

Abstract

BackgroundRecent evidence indicates that microRNAs (miRNAs) can function as tumor suppressors and oncogenes. Single nucleotide polymorphisms (SNPs) at miRNA genes can influence the maturation of miRNAs or miRNA-mediated transcriptional regulation. Our objective was to investigate the association of SNPs in deregulated miRNAs with clinical outcome in patients with non-small cell lung cancer (NSCLC) in a Chinese population.MethodsDeregulated miRNAs in NSCLC and their SNPs were identified through public databases. A single SNP, rs895819 in pre-miR-27a, was found suitable for selection. TaqMan assays were performed for genotyping and to assess the effect on the overall survival (OS) and chemotherapy response in 576 NSCLC patients.ResultsLog-rank test and Cox regression analysis indicated that the G allele of rs895819 was associated with shorter survival and increased risk of death in NSCLC [dominant model: 22.0 vs. 46.0 months, P<0.001; adjusted hazard ratio (HR) = 1.71, 95% confidential interval (CI): 1.12–2.26]. Further stepwise regression analysis suggested that this SNP was an independently unfavorable factor for the prognosis of NSCLC and the effect remained significant in subgroup analysis stratified by clinical parameters and treatment status. Moreover, multivariate logistic regression analysis showed that the subjects with AG/GG genotypes of rs895819 had significantly decreased response rate to platinum-based chemotherapy compared to those with the AA genotype.ConclusionOur results suggest that the pre-miR-27a rs895819 polymorphism may influence NSCLC patients’ clinical outcome. Further large sample studies should be used to validate our findings.

Polymorphisms inMIR27AAssociated with Early-Onset Toxicity in Fluoropyrimidine-Based Chemotherapy

“…Consistent with this supposition, the high-expression miR-27a variant rs895819G has been associated with reduced survival in patients with lung and gastric cancer (19,20). Furthermore, increased miR27a levels have been observed in chemotherapy resistant tumors (12)(13)(14) and suppression of miR-27a has been shown to increase the sensitivity of cancer cell lines to 5FU and other chemotherapy drugs (14,17,29,31).…”

“…Several studies have identified miR-27a as an indirect regulator of the drug efflux pump multidrug resistance protein 1 (MDR1), suggesting a possible mechanism for its observed role in chemotherapy resistance (14,16,17). A common polymorphism (rs895819A>G) in the genomic region encoding miR-27a (MIR27A) has been associated with cancer risk (15,18) and survival in patients with gastric and lung cancer (19,20). In recent functional studies, the G allele was associated with higher levels of miR-27a and reduced DPD levels (8).…”

A single nucleotide polymorphism in the promoter region of let-7 family is associated with lung cancer risk in Chinese

“…Similarly, Xu et al (2013b) found that the G allele of rs895819 in pre-miR-27a was associated with shortened survival time of NSCLC patients. Additionally, the AG/GG genotype exhibited a lower response rate to chemotherapy than the AA genotype (Xu et al, 2013b). In addition to these SNPs, polymorphisms in the binding site of miRNA also play an important role in lung cancer occurrence and survival.…”

“…Among SNPs in pre-miRNAs, studies have reported that the variant homozygote CC of miR-196a2 rs11614913 was an important genotype that was significantly related to an increased risk and poorer survival of lung cancer (Hu et al, 2008;Tian et al, 2009). Similarly, Xu et al (2013b) found that the G allele of rs895819 in pre-miR-27a was associated with shortened survival time of NSCLC patients. Additionally, the AG/GG genotype exhibited a lower response rate to chemotherapy than the AA genotype (Xu et al, 2013b).…”

Association of a Pre-miR-27a Polymorphism with Cancer Risk: an Updated Meta-analysis

“…Out of the Twenty-five, seven articles were pooled analysis, commentary and review papers (Wang et al, 2012;Yang and Burwinkel, 2012;Ma et al, 2013;Wang et al, 2013;Xu et al, 2013b;Zhong et al, 2013;Chen et al, 2014), and four reports were cancer biology experimental studies (Hirota et al, 2012;Jahid et al, 2012;Zanetti et al, 2012;Yuan et al, 2013). Three studies were excluded given that they did not include controls (Yoon et al, 2012;Xu et al, 2013a), or reported non-cancer disease (Song et al, 2013). We also included five eligible articles by manual searching (Li, 2011;Zhang, 2011;Zhang, 2012;Xu et al, 2013b;Kupcinskas et al, 2014), in which the study by Li et al included two independent case-control studies (Li, 2011) and the pooled analysis by Xu et al included one unpublished paper with efficient case-control study data (Xu et al, 2013b).…”