线粒体DNA D-loop区多态性与肝癌预后的研究

目的通过对线粒体DNA D-loop区的碱基测序,了解其多态性及突变情况,并探讨其与肝癌发病机率及预后的关系。方法提取49个乙型肝炎后肝癌病人的肝癌组织,癌旁组织和血液中的线粒体DNA,用测序法测定线粒体DNA D-loop区的碱基序列,了解其单核苷酸多态性和变异情况,并分析其与肝癌发病率及2年生存率的关系。结果通过观察发现,肝癌病mt DNA突变情况与肝癌预后无明确相关,而1个SNP位点(核苷酸150C/T)与肝癌的生存期之间存在统计学上的显著差异。经COX回归分析,发现150位点为肝癌预后的独立危险因素;150C的患者生存期显著短于150T的生存期(相对危险度,0.246;95%CI,0.070-0.861;P=0.028)。结论通过分析在线粒体DNAD-loop区的多态性,可以帮助筛别预后不良的肝癌患者。

Investigation of the association between mitochondrial D-loop polymorphisms and hepatocellular carcinoma outcome

Objective To investigate the accumulation of mutations and single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) might be associated with cancer risk and disease outcome. Methods We obtained cancerous and noncancerous liver tissues from 49 HBV-related HCC patients at the Fourth Hospital of Hebei Medical University. mtDNA of the liver tissues was extracted with Mitochondrial DNA Extraction Kit. Mutation and polymorphism were confirmed by repeated analysis. We assessed the prediction power of D-loop SNPs in hepatocellular carcinoma (HCC) patients. Results No mutation in these HCC patients had prediction power for post-operational survival, whereas one SNP site (nucleotide 150 C/T) was identified by the log-rank test for statistically significant prediction of HCC survival. In an overall multivariate analysis, allele 150 was identified as an independent predictor of HCC outcome. The length of survival of patients with allele 150C was significantly shorter than that of patients with allele 150T (relative risk, 0.246; 95% CI, 0.070-0.861; P=0.028). Conclusions The analysis of genetic polymorphisms in the mitochondrial D-loop helps to identify patient subgroups at high risk of a poor disease outcome.