CAGE MAGE-A1和MAGE-A3去甲基化在胃癌发生发展中的作用

Role of DNA Demethylation of Promoter CpG island of CAGE,MAGE-A1,and MAGE-A3 in Early Carcinogenesis and Progression of Human Gastric Carcinoma

目的:探讨肿瘤相关抗原基因(CAGE)、黑色素瘤抗原基因-A1(MAGE-A1)和黑色素瘤抗原基因-A3(MAGE-A3)启动子区去甲基化状态改变在胃癌早期发生、发展中的作用及意义。方法:87例内镜活检标本分为胃癌组、癌前病变组和正常对照组,应用甲基化特异性PCR方法分别检测各组中3种基因启动子区的去甲基化状态。结果:胃癌组、癌前病变组和正常对照组中,各基因启动子区的去甲基化阳性率分别为:CAGE:80.0%(24/30)、37.5%(12/32)和4.0%(1/25);MAGE-A1:60.0%(18/30)、21.9%(7/32)和0(0/25);MAGE-A3:46.7%(14/30)、12.5%(4/32)和8.0%(2/25),呈下降趋势。3种基因启动子区去甲基化阳性率在3组间比较,差异有统计学意义(P<0.05)。30例胃癌至少发生1种基因启动子区去甲基化的有27例;至少发生2种基因启动子区去甲基化23例;7例同时发生了3种基因启动子区的去甲基化。结论:这3种基因启动子区去甲基化改变可能发生于胃癌发病早期,且贯穿于胃癌发生、发展的全过程并起到一定的作用,联合检测可能有助于提高胃癌去甲基化诊断的阳性率。

Objective： To investigate the role of DNA promoter demethylation of cancer-related antigen gene （ CAGE ）, melanoma antigen gene A1 （ MAGE-A1 ）, and melanoma antigen gene A3 （ MAGE-A3 ） in early carcinogenesis and advanced-stage gastric carcinoma. Methods： A total of 87 fresh samples were collected from patients who underwent gastric endoscopy. The samples were divided into three groups based on pathological results, namely, gastric carcinoma, premalignant lesions, and normal control. Demethylation of CAGE, MAGE-A1, and MAGE-A3 promoter areas in each group was determined using the methylation-specific polymerase chain reaction. Results： The positive rates of demethylation of the three genes in the gastric carcinoma, premalignant lesion, and normal control groups, were as follows： CAGE： 80.0% （ 24/30 ）, 37.5% （ 12/32 ）, and 4.0% （ 1/25 ）, respectively; MAGE-AI： 60.0% （ 18/30 ）, 21.9% （ 7/32 ）, respectively, and 0 （ 0/25 ）; and MAGE-A3： 46.7% （ 14/30 ）, 12.5% （ 4/32 ）, and 8% （ 2/25 ）, respectively. Hypomethylation of CAGE, MAGE-A1, and MAGE-A3 promoter areas significantly decreased one by one from gastric carcinoma to premalignant lesion to normal mucosa. There was statistical significance when the three genes were compared among the three groups （ P 〈 0.05 ）. Of the 30 cases with gastric carcinoma, hypomethylation of at least one gene promoter area occurred in 27 cases, at least two gene promoters were found in 23, and all three gene promoters were found in 7. Conclusion： Changes in the demethylation of CAGE, MAGE-AI, and MAGE-A3 promoter areas may occur in the early stage of carcinogenesis. This process plays a role in the occurrence and progression of gastric cancer. The combined detection for the demethylation of a gene promoter may enhance the efficiency of detecting hypomethylation in gastric cancer.