Significance of detection of multigene methylation in liver cancer tissue for early diagnosis of liver cancer
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摘要:
目的检测肝癌患者癌组织中p14、p15、p16、RB基因启动子异常甲基化状况,探讨其在肝癌诊断中的价值。方法采用甲基化特异性PCR(MSP)方法检测44例肝癌组织及其相对应41例肝硬化组织、44例癌旁组织中p14、p15、p16、RB的甲基化状况。对所得结果进行卡方检验,Fisher精准概率分析。结果肝硬化组织中p14、p15、p16、RB 4种基因的甲基化检出率分别为17.1%(7/41)、28.9%(11/41)、36.6%(15/41)和7.3%(3/41);肝癌组织中4种基因的甲基化检出率分别为34.1%(15/44),56.8%(25/44),70.5%(31/44)和27.3%(12/44)。癌旁组织中检测出p16甲基化阳性产物4例,p15阳性产物1例。癌组织和肝硬化组织中4种基因的甲基化率明显高于癌旁组织(P<0.05);不同年龄、性别、肿瘤分化程度和临床分期的肝癌患者各个基因甲基化率没有明显差异。结论 p14、p15、p16、RB基因甲基化在肝癌中频发;多基因甲基化的联合检测在肝癌的早期诊断中有一定的价值。
Abstract:Objective To evaluate the abnormal methylation of p14, p15, p16, and RB in the cancerous tissues of liver cancer patients and to investigate the significance of detection of multigene methylation for the early diagnosis of liver cancer. Methods Methylation-specific PCR was used to evaluate the methylation status of p14, p15, p16, and RB in the cancerous tissues of 44 liver cancer cases and the cirrhotic tissues of 41 liver cirrhosis cases as well as the paracancerous tissues of the 44 liver cancer cases. The obtained data were subjected to chi-square test and Fisher′s exact test. Results Among the 41 liver cirrhosis cases, the methylation of p14, p15, p16, and RB was detected in 7 cases (17.1%), 11 cases (28.9%), 15 cases (36.6%), and 3 cases (7.3%), respectively. Among the 44 liver cancer cases, the methylation of p14, p15, p16, and RB was detected in 15 cases (34.1%), 25 cases (56.8%), 31 cases (70.5%), and 12 cases (273%), respectively. In the 44 paracancerous tissues, p16 methylation was detected in 4 cases, and p15 methylation in 1 case. The methylation rates of the four genes were significantly higher in liver cancer tissues and liver cirrhosis tissues than in paracancerous tissues (P<0.05). There were no significant differences in the methylation rates of the four genes among liver cancer patients with different ages, sexes, degrees of tumor differentiation, and clinical stages (P>0.05). Conclusion The methylation of p14, p15, p16, and RB is frequent in the pathogenesis of liver cancer. The detection of multigene methylation is of certain significance for early diagnosis of liver cancer.
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