胶质瘤患者外周血 DNA 修复基因甲基化与蛋白表达的相关性

摘要

目的：探讨胶质瘤患者O6-甲基鸟嘌呤-DNA-甲基转移酶（ O6-Methylguanine -DNA methyltransferase，MGMT）及人类错配修复基因 MSH2（Human mutS homolog2，hMSH2）蛋白表达与外周血相应基因启动子甲基化的相关性。方法分别采用免疫组化法及甲基化特异性PCR （ MSP ）检测275例胶质瘤患者肿瘤组织MGMT、hMSH2蛋白的表达及外周血中这两个基因启动子甲基化情况。结果脑胶质瘤患者肿瘤组织MGMT和hMSH2蛋白阴性表达率分别为47．2％和62．5％；基因启动子区甲基化阳性率分别为41．8％和22．4％。统计学分析显示外周血MGMT基因启动子甲基化与肿瘤组织蛋白阴性表达相关（P＜0．05）。 hMSH2基因启动子甲基化与肿瘤组织hMSH2蛋白表达不具有相关性（P＞0．05）。结论 MGMT基因甲基化是脑胶质瘤发生过程中常见的分子事件，可能与胶质瘤的发生有关；而hMSH2基因启动子甲基化可能并不是胶质瘤hMSH2蛋白失活的主要原因，可能存在其他重要因素影响其表达。%Objective To investigate the relevance between protein expression and methylation of MG-MT and hMSH2 in glioma patimts.Methods Immunohistochemical and methylation specific PCR were adopted respectively to test on 275 cases of glioma patients for the protein expression and methylation situation of MGMT and hMSH2.Results The negative protein expression rate of MGMT and hMSH 2 in the tissue of brain golima were 47.2% and 62.5% respectively;the occurrence of methylation in gene promoter region were accordingly 41.8% and 22.4%.Statistical analysis revealed that MGMT promoter methylation in peripheral blood gene groups was related with the protein negative expression of tumor tissue (P<0.05),while there was no relationship between the protein expression of hMSH2 and its gene promoter methylation(P>0.05).Conclusion The meth-ylation of MGMT is a common molecular situation in the generation of brain glioma ,which may be connected with that of tumor.However,hMSH2 promoter methylation might not the main reason for inactivation of hMSH 2 pro-tein,there may be other important factors affecting its expression .