TIMP-3基因甲基化调控与大肠癌发生发展的关系研究

摘要

Objective: To explore whether aberrant methylation in the promoter of TIMP-3 gene was associated with carcinogenesis and clinicopathological characteristics of colon cancer.Methods:Forty five colon cancer specimens,48 specimens of no tumor disease in colon,42 adenoma specimens were collected at random.The 5' CpG islands' methylation status of TIMP-3 gene were detected by methylation-specific PCR (MSP).Results:The status of CpG islands methylation of TIMP-3 gene promoter region were higher in colon cancer group than the group of no tumor disease in colon (P＜0.01)and adenoma group(P＜0.05),were higher in adenoma group than the group of no tumor disease in colon(P＜0.05).The status of CpG islands methylation of TIMP-3 gene promoter region were higher in the groups of lymph node metastasis ,hepatic metastasis and Duck's C+D than in the groups no lymph node metastasis,no hepatic metastasis and Duck's A+B (P＜0.01).Conclusion:The status of CpG islands methylation of TIMP-3 gene promoter region play important role in carcinogenesis and development of colon cancer,It is valuble in the early preventment,diagnosis and prognosis of colon cancer.%目的:探讨TIMP-3甲基化调控与大肠癌发生发展的关系.方法:随机收集45例大肠癌病例、42例大肠腺瘤病例、48例非肿瘤性大肠病例标本,用甲基化特异性PCR(methylation-specific PCR,MSP)分别检测TIMP-3基因启动子5'CpG岛甲基化状况.结果:非肿瘤性大肠病变、大肠腺瘤、大肠癌分别有0例 (0.00%)、5例 (11.90%)、14例(31.11%)TIMP-3基因启动子发生甲基化.大肠癌组织TIMP-3甲基化率高于非肿瘤性大肠病变(P＜ 0.01)和大肠腺瘤(P＜ 0.05).大肠腺瘤TIMP-3甲基化率高于非肿瘤性大肠病变(P＜ 0.05).大肠癌肝转移组、淋巴结转移组TIMP-3基因甲基化率分别高于非肝转移组(P＜ 0.01)、非淋巴结转移组(P＜ 0.01);Duck's C+D组甲基化率分别高于Duck's A+B组(P＜ 0.01).结论:大肠癌TIMP-3基因的高甲基化在大肠癌的发生、发展中发挥重要作用,对于大肠癌的早期预防、诊断、恶性程度及预后判断有重要意义.