TIMP-3基因甲基化调控与大肠癌发生发展的关系研究

Correlation of the methylation status of TIMP-3 gene promoter with carcinogenesis and development of human 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'sC+D组甲基化率分别高于Duck'sA+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。

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 ＇FIMP -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 metasta- sis, 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.