胃癌血清肿瘤相关基因超甲基化检测及其意义

Detection of Promoter Hypermethylation in Tmor-related Genes and Its Significance in Gastric Cancer

目的:探讨检测胃癌患者血清中肿瘤相关基因超甲基化的可行性及其意义。肿瘤患者的血清中游离DNA存在质或量的变化,是可能的肿瘤标志物。DNA甲基化不改变DNA序列和遗传密码,具有可逆性,被认为是基因转录调控的表观遗传机制之一。抑癌基因启动子超甲基化通常导致基因的转录失活,其功能的丧失,参与肿瘤的发生。方法:通过甲基化特异性PCR(MSP)检测52例胃癌组织和配对血清的hMLH1、E-cadherin、GSTP1、p15和p16基因的启动子超甲基化。20例健康体检者血清作为对照。结果:在胃癌组织中检测到hMLH1、E-cadherin、GSTP1、p15和p16基因的启动子超甲基化率分别为28.8%、76.9%、23.1%、59.6%和69.2%;在患者血清中检测到hMLH1、E-cadherin、GSTP1、p15和p16基因的启动子超甲基化率分别为13.5%、38.5%、15.4%、25.0%和30.8%。84.7%的患者血清可以检测到异常甲基化。所有血清中检测到异常甲基化的患者,其肿瘤组织也能检测到相应基因的异常甲基化。对照组血清未检测到任何异常甲基化。结论:MSP检测血清异常甲基化是一种具有较高灵敏度和特异性的方法,可以在大部分胃癌患者血清中同时检测到多个肿瘤相关基因的异常甲基化,可以将其作为胃癌诊断的辅助手段。

Objective： To investigate the feasibility and significance of detecting promoter hypermethylation in tmor-related genes in gastric cancer. Methods： The tissues and serum from 52 gastric cancer patients were detected for abnormal methylation in hMLH1, E-cadherin, GSTP1, p15, and p16 by methylation-specific PCR （MSP）. Serum from 20 age-matched healthy people was adopted as the control. Results： The positive rate of promoter hypermethylation in hMLH1, Ecadherin, GSTP1, p15, and p16 gene were 28.8%, 76.9%, 23.1%, 59.6% and 69.2% in primary tumor tissues, and 13.5%, 38.5%, 15.4%, 25.0% and 30.8% in the serum of gastric cancer patients. Patients with promoter hypermethylation in serum DNA also had promoter hypermethylation in cancer tissues. Overall, 84.7% patients with gastric cancer can be detected with promoter hypermethylation in serum DNA. DNA hypermethylation was not found in the serum of the controls. Conclusion： MSP is a sensitive and specific method to detect gene-promoter methylation in serum. Promoter hypermethylation can be detected in the serum and cancer tissues of most gastric cancer patients. It can be helpful for the diagnosis of gastric cancer.