胃癌HOXB6基因异常甲基化及其表达

Hypermethylation and expression of HOXB6 gene in gastric cancer

目的检测胃癌组织中ＨＯＸＢ６基因是否存在异常甲基化，并探讨其与基因表达及临床因素的关系。方法用联合重硫酸盐限制性分析法（ＣＯＢＲＡ法）对７种胃癌细胞系和７３例胃癌患者的胃镜下活检组织进行ＨＯＸＢ６基因的甲基化定量检测，并采用逆转录聚合酶链反应方法检测基因的表达及脱甲基化处理后基因的再表达。结果７种胃癌细胞系中有４种异常甲基化，在异常甲基化的细胞系基因表达减少或消失，并且脱甲基化处理后基因可以重新表达。７３例胃癌患者的癌部位和非癌部位的活检组织中，２０例癌组织甲基化阳性（２７．４０％），而非癌组织中无１例阳性。结论胃癌中ＨＯＸＢ６基因的异常甲基化与基因表达抑制密切相关，并且脱甲基化后基因可以再表达；胃癌组织中ＨＯＸＢ６基因异常甲基化具有高度特异性，可作为肿瘤标志物用于临床诊断。

Objective To detect the hypermethylation of HOXB6 gene in gastric cancer tissue and investigate the relationship between the gene expression and the clinics.Methods seven types of gastric cancer cell line and 73 cases of gastric cancer biopsy tissues were measured by combined bisulfite restriction analysis method.The gene expression and the re-expression after demethylation were detected by RT-PCR.Results Of 7 cell lines examined, 4 showed hypermethylation.The methylating status of HOXB6 was found to be correlated with loss of expression,which was restored by 5-aza-2＇-deoxycytidine treatment.We also find hypermethylation in 20/73(27.40%)case of cancer tissues but no one in non cancer tissue.Conclusion There are close relationship between hypermethylation and gene silencing in the HOXB6 gene of gastric cancer,There are also a gene re-expression after its demethylation.Hypermethylation of HOXB6 gene can be a tumor marker for gastric cancer diagnosis,and the agent of demethylation maybe a new antineoplastic drug.