caveolin-1、Dnmt1基因与胃癌发生发展的关系及其临床意义

Clinical significance and association of caveolin-1 and Dnmt1 gene with carcinogenesis,development of gastric carcinomas

目的:研究正常胃黏膜及胃癌组织中caveolin-1、Dnmt1蛋白的表达,并探讨caveolin-1、Dnmt1基因与胃癌发生发展的关系及其临床意义.方法:采取甲基化特异性聚合酶链反应(methylation-specific PCR,MSP)检测不同分化程度的60例胃癌组织(其中包括新鲜组织50例、石蜡包埋组织10例)和14例正常胃组织中caveolin-1基因启动子区域甲基化状态;同时用SP免疫组织化学法、原位杂交法检测caveolin-1蛋白、Dnmt1蛋白及mRNA的表达.结果:14例正常胃组织中,未检测到caveolin-1基因甲基化;在60例胃癌组织中,检测到44例胃癌组织中存在甲基化,甲基化发生率为73.33%,两组间差异具有统计学意义(P<0.005).caveolin-1基因甲基化的发生与患者年龄有关.60例胃癌标本中,caveolin-1蛋白阳性表达率仅为30%(18/60),Dnmt1蛋白阳性表达率为63.3%(38/60),Dnmt1基因mRNA阳性表达率为53.3%(32/60).结论:在胃癌组织中,caveolin-1基因可能在Dnmt1基因的作用下发生甲基化,丧失其活性,进而导致胃癌的发生、发展.

AIM： To investigate the expression of caveolinland Dnmtl genes in normal gastric mucosa and gastric carcinoma, and to detect methylation status of CpG island of caveolin-1 gene promoter region located in exon i and its clinical significance in gastric carcinoma. METHODS： Methylation status of caveolin-1 gene in 60 gastric carcinoma cases and 14 normal gastric tissues was detected using Methylationspecific PCR （MSP）. SP immunohistochemcal method and in site hybridization （ISH） wereused to detect the expression of caveolin-1 protein and Dnmtl protein and mRNA. RESULTS： The methylation rate of the 5＇ CpG island of caveolin-1 gene was 0% in 14 normal gastric tissues, and 73.3% in 60 gastric carcinoma cases. There was significant difference between two groups （P 〈 0.005）. Methylation status of caveolin-1 gene was related to the patient＇s age. The positive rates of caveolin-1 protein, Dnmtl protein and mRNA were 30%, 63.3% and 53.3% in 60 gastric carcinoma cases. CONCLUSION： The methylation and inactivation of caveolin-1 gene leads to carcinogenesis and development of gastric carcinomas by the function of Dnmtl gene.