肝癌c-fms癌基因甲基化水平与临床病理关系

Methylation status of c-fms oncogene in hepatocellular carcinoma and its relation with clinical pathology

目的观察肝癌发生过程中 ｃ－ｆｍｓ癌基因甲基化水平的变化，以阐明 Ｃ—ｆｍｓ／ＣＳＦ一１Ｒ 集落刺激因子－１受体）在肝癌组织中的异常高表达机制。方法采用限制性内切酶 Ｈｐａ Ⅱ／Ｍｓｐ Ⅰ酶切 ３０例肝癌及配对的癌旁肝组织基因组ＤＮＡ，Ｓｏｕｔｈｅｒｎ杂交法检测其甲基化状态。比较肝癌及癌旁肝组织中ｃ－ｆｍｓ癌基因甲基化水平，判断其与临床病理学的关系。结果３６．７％（１１／３０）肝癌组织及１３．３％（４／３０）癌旁肝组织中ｃ－ｆｍｓ癌基因甲基化水平降低。ｃ－ｆｍｓ癌基因在肝癌组织中的低甲基化发生率高于癌旁肝组织。Ｅｄｍｏｎｄｓｏｎ分级与肝癌组织中ｃ－ｆｍｓ癌基因低甲基化发生率有显著性意义，Ⅲ～Ⅳ级发生率明显高于Ⅰ～Ⅱ级。结论ｃ－ｆｍｓ癌基因低甲基化改变导致ＣＳＦ－１Ｒ异常高表达，可能是促使肝癌发生和发展的重要分子生物学机制。

Objective To study the methylation status change of c-fms oncogene in hepatocellular carcinogenesis, and to clarify the abnormal highly expressing mechanism of c-fms/CSF-1R in hepatocellular carcinoma(HCC). Methods Genome DNA of 30 cases of HCC tissue and matching surrounding-cancer tissue were digested with restrictive endonucleases Hpa II /Msp I. Methylation status of c-fms oncogene was tested with Southern blot. Methylation status of c-fms oncogene in the HCC tissue and the matching surrounding-cancer tissue was compared. The relation between methylation status of c-fms oncogene and clinical pathology of HCC was determined. Results Methylation status of c-fms oncogene decreased in 36.7%(11/30) HCC tissue and 13.3%(4130) matching surrounding-cancer tissue. The hypomethylation rate of c-fms oncogene in the HCC tissue was higher than that in the matching surrounding-cancer tissue. There was significant correlation between Edmondson scale of HCC and hypomethylation of c-fms oncogene. The hypomethylation rate of HCC in Edmondson III^IV was higher than that in Edmondson I ~II. conclusions Hypomethylation of c-fms oncogene may be an important molecular mechanism leading to abnormally high expressing of CSF-1R, which contributes to occurrence and deterioration of HCC.