hMLH1、hMSH2单核苷酸多态性与NSCLC铂类药物化疗后生存期的关系

Relationship of hMLH1 and hMSH2 single nucleotide polymorphisms and survival in patients with advanced non-small cell lung cancer after platinum-based chemotherapy

目的探讨hMLH1、hMSH2单核苷酸多态性(SNPs)与非小细胞肺癌(NSCLC)铂类为主的方案化疗后生存期的关系。方法经病理学确诊的晚期NSCLC患者120例,采用铂类为主的两药联合化疗方案,化疗前采集患者的外周血。根据cDNA芯片原理制作目的基因芯片,利用双色荧光探针杂交进行多态性的基因分型,并随机抽取10%的样本进行测序来验证该方法的准确性,比较不同基因型与铂类药物化疗后生存期的关系。结果成功进行基因分型,野生型、杂合型和突变型的叠加荧光分别显示为绿色、黄色和红色,与基因测序结果完全吻合。中位随访11个月。携带hMLH1 T/T和T/A+A/A基因型患者铂类化疗后中位生存期(MST)为11.2个月和14.2个月,1年、2年、3年生存率分别为40.5%、11.9%、7.1%和63.6%、9.1%、4.5%(P>0.05);携带hMSH2 T/T和T/C+C/C基因型患者MST、1年生存率分别为13.4个月、57.7%和10.7个月、33.3%(P<0.05),2年及3年生存率差异均无统计学意义(P>0.05)。结论 hMLH1、hMSH2基因多态性与NSCLC患者铂类药物化疗后的生存期无显著相关性。

Objective To investigate the relationship between single nucleotide polymorphisms of hMLH1 and hMSH2 and survival time of patients with advanced non-small cell lung cancer（NSCLC） after platinum-based chemotherapy.Methods A total of 120 patients with advanced NSCLC were routinely treated by platinum-based chemotherapy.The polymorphic genotypes were analyzed by gene-chip method using DNA samples isolated from peripheral blood before treatment.Besides,10% samples were extracted randomly for sequencing to test the accuracy of this method.The relationship between genetic polymorphisms of hMLH1 and hMSH2 and survival was compared.Results Homozygous wild type,heterozygote type and homozygous mutant type yielded green,yellow and red fluorescence,respectively.The results were accordant with gene sequencing.Median follow-up period was 11 months.Median survival time（MST）,1-year survival,2-year survival and 3-year survival rates were 11.2 months,40.5%,11.9% and 7.1% for patients with the hMLH1 T/T genotype,and 14.2 months,63.6%,9.1% and 4.5% for those with T/A＋A/A genotype（P〈0.05）.MST and 1-year survival rate of patients with the hMSH2 T/T genotype were 13.4 months and 57.7%,which were more than 10.7 months and 33.3% of those with T/C＋C/C genotype（P〈0.05）.There were no significant differences in 2-year and 3-year survival rates between the patients with the hMSH2 T/T genotype and those with T/C＋C/C genotype（P〈0.05）.ConclusionPolymorphisms of hMLH1 and hMSH2 genes may have no association with overall survival period in the patients with advanced NSCLC after treated with platinum-based chemotherapy.