【摘要】 目的:为探讨错配修复基因hMSH2与人群肺癌发病的关系而进行本研究。方法:用RT-PCR技术检测150例肺癌组织、40例正常肺组织、50对肺癌病例和对照外周血单个核细胞中hMSH2基因的mRNA表达;用免疫组化检测P53、C-MYC、K-RAS、BCL-2和hTERT等基因的蛋白表达;并分析有关暴露因素和肺癌的临床特征对修复基因hMSH2表达的影响,以及hMSH2基因与P53、C-MYC、K-RAS、BCL-2和hTERT等癌变相关基因的关系;用Logistic回归模型分析上述基因在肺癌发病中的作用。结果:32.0％(48/150)的肺癌组织和5.0％(2/40)的正常肺组织存在hMSH2基因表达低下;16.0％(8/50)的肺癌病人外周血和2％(1/50)的正常人外周血单个核细胞也可检出hMSH2基因表达低下。分析各种暴露因素和临床特征对hMSH2基因表达的影响,未发现与该基因表达相关的因素。但发现P53突变蛋白的过度表达与hMSH2表达低下有一定的关联,P值为0.02。hMSH2与C-MYC、K-RAS、BCL-2和hTERT基因的表达无显著性关系,P皆>0.05。多因素Logistic回归分析表明,吸烟、P53突变蛋白、K-RAS癌基因蛋白和hTERT基因的过度表达是肺癌的危险因素,DNA修复基因hMSH2的正常表达是肺癌的保护因素,调整性别、年龄、吸烟状态和其他基因的影响后,hMSH2表达低下与发生肺癌的危险度OR值为9.17(1.31,64.09)更多还原

【Abstract】 Objective;To investigate the relationship between DNA mismatch repair gene hMSH2 and the development of human lung cancer. Methods The reverse transcription-polymerase chain reaction ( RT-PCR) method was applied to measure hMSH2 mRNA expression in 150 cases of human lung cancer tissues,40 normal lung tissues, and in the peripheral mononuclear blood cells from 50 lung cancer cases and 50 normal controls. The protein expressions of P53 ,C-MYC, K-RAS, BCL -2 and hTERT (human telomerase reverse transcriptase) were assessed by immuno-histochemistry. The associations of some exposure factors and clinical characteristics with the expression of hMSH2 gene were analyzed. The relationships between hMSH2 gene and cancer related genes P53 ,C-MYC,K-RAS,BCL -2 and hTERT were investigated. Logistic regression models were used to analyze the effects of these genes on lung cancer. Result The expression of hMSH2 was low or absent in 48 of 150(32. 0% ) lung cancer specimens,whereas only in 2 of 40 (5. 0% ) normal lung tissues reduced levels of hMSH2 expression were observed. Reduced expression levels of hMSH2 were observed in 8 of 50 ( 16. 0% ) lung cancer patients’ peripheral mononuclear blood cells,and 1 of 50 (2.0% ) normal controls’ blood cells. We tried to investigate the exposure factors to see if any one affects the expression of hMSH2 gene,but no factor showed correlated with hMSH2. The over-expression of P53 was moderately correlated with the low expression of hMSH2(P =0. 02) ; but the expressions of K-RAS, C-MYC, BCL -2 and hTERT were not correlated with the status of hMSH2 gene,P values were >0. 05. In the multivariate Logistic model, smoking, mutation of P53 ,over-expression of K-RAS oncogene and hTERT genes were risk factors of human lung cancer. By controlling the confounding of sex, age, smoking status and other genes, it showed that low expression of DNA repair gene hMSH2 was a risk factor for human lung cancer, the OR was 9.17(1.31,64.09),P = 0. 035. Conclusion The normal expression of DNA repair gene hMSH2 might play an important protective role in the development of human lung caner, and the low expression of hMSH2 could be used as a valuable susceptibility biomarker of human lung cancer.更多还原