ATM基因CpG岛甲基化与食管鳞癌易感性的相关性研究  

Association of ATM gene CpG island methylation with susceptibility to esophageal squamous cell carcinoma

作　　者：樊卫[1] 祁金友[1] 郑羽[2] 杨峥[3] FAN Wei;QI Jin-you;ZHENG Yu(Clinical Laboratory;Department of Oncology,Huai＇an Tumor Hospital,Huai＇an Jiangsu 223200,China.)

机构地区：[1]淮安市肿瘤医院检验科,江苏淮安223200 [2]淮安市肿瘤医院肿瘤科,江苏淮安223200 [3]淮安市肿瘤医院胸外科,江苏淮安223200

出　　处：《临床和实验医学杂志》2018年第18期1955-1958,共4页Journal of Clinical and Experimental Medicine

基　　金：淮安市应用研究与科技攻关(社会发展)计划项目(编号:HAS2014002)

摘　　要：目的探讨ATM基因CpG岛甲基化与食管鳞癌易感性的相关性。方法应用亚硫酸氢盐测序PCR(BSP)联合TA克隆测序检测240例食管鳞癌患者组与170例体检健康对照组血浆ATM基因CpG岛甲基化情况;选取前述240例食管鳞癌患者组中的40例食管鳞癌患者标本的食管鳞癌癌变组织和癌旁正常组织,采用经典的免疫组化SP法进行ATM蛋白检测。应用相关性分析ATM基因CpG岛甲基化与ATM蛋白表达阴性的关联。结果具有吸烟习惯者患食管鳞癌危险性显著高于不吸烟者(P<0.05);有肿瘤家族史者患食管鳞癌危险性显著高于无肿瘤家族史者(P<0.05);240例食管鳞癌患者组CpG岛甲基化阳性率为88.67%,体检健康组CpG岛甲基化阳性率为73.59%,食管鳞癌患者组CpG岛甲基化阳性率明显高于体检健康对照组,差异具有统计学意义(P<0.05)。在40例食管鳞癌癌变组织中有25例ATM蛋白表达为阳性,在40例相应的癌旁正常组织中有38例ATM蛋白表达为阳性,两组差异具有统计学意义(P<0.05),并且ATM基因CpG岛甲基化率与癌变组织ATM蛋白表达阴性结果具有很好的相关性(r=0.994)。结论 ATM基因CpG岛高度甲基化状态导致其蛋白表达下调,表明其可能为抑制ATM蛋白表达的重要因素;ATM基因CpG岛高度甲基化可能为食管鳞癌发生、发展的一个重要的分子生物学事件。Objective To investigate the association of ATM gene CpG island methylation with susceptibility to esophageal squamous cell carcinoma（ESCC）. Methods The CpG island methylation of ATM gene was detected in 240 patients with ESCC and 170 healthy controls by bisulfite sequencing PCR（BSP） and TA cloning sequencing. The expression of ATM protein was detected by Streptavidin Perosidase（SP） immunohistochemical staining for the 40 samples from ESCC patients containing cancerous tissue and adjacent normal tissue. The chi-square test was used to compare the rate of each group,and P〈0. 05 for the difference was statistically significant. The correlation between CpG island methylation of ATM gene and negative ATM protein was analyzed by correlation analysis. Results The risk of ESCC with smoking habits was significantly higher than that of non-smokers（P〈0. 05）. The risk of ESCC with family history of cancer was significantly higher than that without family history（P〈0. 05）. The positive rate of methylation of CpG island 88. 67% in ESCC was significantly higher than that in healthy control group Group 73. 59%（P〈0. 05）. 25 in 40 cases of ATM protein expression was positive in cancerous tissues while 38 positive in corresponding normal tissues and the difference between the two groups was statistically significant（P〈0. 05）. The CpG island methylation rate of ATM gene had a good correlation with the negative result of ATM protein expression in cancerous tissues（r = 0. 994）. Conclusion The hypermethylation of CpG island of ATM gene resulted in down-regulation of ATM protein expression,indicating that it may be an important factor in inhibiting ATM protein expression. The hypermethylation of CpG island of ATM gene may be an important molecular biological event for the occurrence and development of ESCC.

关 键 词：食管鳞癌 CPG岛甲基化 亚硫酸氢盐测序PCR ATM基因 ATM蛋白 

分 类 号：R735.1[医药卫生—肿瘤]