miR-124 rs531564、miR-26A rs7372209和miR-126 rs4636297基因多态性与结直肠癌患者预后的相关性研究

Correlation analysis of miR-124 rs531564,miR-26A rs7372209 and miR-126 rs4636297 polymorphisms to the prognosis of colorectal cancer

目的评估微RNA(miR)-124、miR-26A和miR-126基因单核苷酸多态性(SNP)对结直肠癌(CRC)患者预后的影响。方法以2011年7月至2013年12月该院收治的724例CRC住院患者为研究对象,利用PCR-连接酶检测反应(PCR-LDR)技术对患者外周血miR-124rs531564、miR-26Ars7372209和miR-126rs4636297进行SNPs位点基因型分析。患者的总生存时间(OS)和无复发生存率(PFS)采用Kaplan-Meier法计算,单变量log-rank法比较SNPs不同的基因型和单倍体型对OS和RFS的影响。结果携带miR-124rs531564CG基因型的CRC患者手术治疗后3年内OS较携带CC基因型的患者缩短,3年内因肿瘤死亡风险增加[HR2=1.450,95%CI(1.043~2.017),P=0.026];携带GG基因型的患者较携带CC型的患者3年内因肿瘤死亡风险亦增加[HR2=2.339,95%CI(1.171~4.674),P=0.024];在显性基因模型中,携带CG+GG基因型的患者较携带CC基因型的患者预后3年内OS明显下降[HR2=1.532,95%CI(1.119~2.096),P=0.008];隐性基因模型中,携带GG基因型与携带CC+CG基因型患者的OS无明显差异[HR2=1.975,95%CI(1.000~3.900),P=0.052];共显性模型中,以CC+CG基因型为参照,携带CG基因型的患者OS降低,患者3年内因肿瘤死亡风险增加[HR2=1.395,95%CI(1.007~1.931)]。未发现miR-26Ars7372209位点和miR-126rs 4636297位点基因多态性与CRC术后3年内OS和RFS相关(P>0.05)。结论miR-124rs531564位点基因多态性是CRC患者预后的独立影响因素。

Objective To assess the influence of miRNA（miR）-124,miR-26 Aand miR-126 single nucleotide polymorphism（SNPs）on the prognosis in patients with colorectal cancer（CRC）.Methods A total of 724 cases of patients with CRC treated in this hospital from July 2011 to December 2013 served as the research subjects.The peripheral blood samples were collected,and genotype analysis of miR-124 rs531564,miR-26 Ars7372209 and miR-126 rs4636297 SNPs locus were performed by using the PCRLDR.The patient′s overall survival（OS）and progression-free survival（PFS）were calculated by using Kaplan-Meier method,and the univariate log-rank method was used to analyse the influence of different genotypes and haplotypes of SNPs on OS and PFS.Results The OS after operation in CRC patient′s carrying miR-124 rs531564 CG genotype was decreased compared with that in patients carrying CC genotype,and the patient′s death risk was increased[HR2=1.450,95%CI（1.043-2.017）,P=0.026];the patient′s death risk in patients carrying GG genotype was also increased compared with that in patients carrying CC genotype[HR2=2.339,95%CI（1.171-4.674）];in the dominant gene model,the OS in patients carrying CG＋GG genotype was significantly decreased compared with patients carrying CC genotype[HR2=1.532,95%CI（1.119-2.096）,P=0.008];in the recessive gene model,no statistically significant difference was found in OS between patients carrying GG genotype and those carrying CC＋CG genotype[HR2=1.975,95%CI（1.000-3.900）,P=0.0052];in the co-dominant model,compared with patients carrying CC＋CG genotype,the OS in patients carrying CG genotype was decreased and their death risk was increased[HR2=1.395,95%CI（1.007-1.931）].There was no correlation of miR-26 Ars7372209 locus and miR-126 rs4636297 locus gene SNPS to OS and PFS in CRC patients（P〉0.05）.Conclusion miR-124 rs531564 gene polymorphism might be an independent influence factor of the prognosis in CRC patients.