卵巢癌中ASC基因表达缺陷与其甲基化的关系

Relationship between Expression Defect and Methylation of ASC Gene in Ovarian Cancer

目的探讨ASC(apoptosis-associated speck-like protein containing CARD)基因在卵巢组织中的表达,并分析其临床意义及其表达缺陷与基因甲基化的关系。方法以18例卵巢癌组织和8例正常卵巢组织、8例卵巢良性肿瘤作为研究对象,采用甲基化特异性PCR(methylation specific PCR,MSP)检测卵巢组织中ASC基因启动子区域甲基化的状态,用RT-PCR和免疫组织化学SP法分别检测其mRNA和蛋白的表达。结果在正常卵巢和卵巢良性肿瘤组织中均未扩增出甲基化条带,在卵巢癌组织中,ASC基因甲基化率为38.9%(7/18)。在正常卵巢组织、卵巢良性肿瘤组织和卵巢癌组织中,ASC基因mRNA和蛋白的表达强度依次下降,其中发生甲基化组织的mRNA和蛋白的表达明显低于未发生甲基化的组织。ASC蛋白在高中分化的卵巢癌组织中的表达明显高于低分化组织。结论卵巢癌中存在ASC基因甲基化,这可能是导致该基因沉默的原因之一,且在卵巢癌的发病机制中起作用。

Objective To study the expression of ASC gene in ovarian tissues and the clinical value,and analyze the relationship between ASC gene expression defect and its methylation. Methods Genomic DNA was isolated from 18 cases of primary ovarian cancer,8 cases of normal ovary tissues and 8 cases of ovarian benign tumor specimens. Methylation specific PCR was used to detect methylation of ASC promotor region.＂ The expression of ASC mRNA and protein was examined by RT-PCR and immunohistochemistry. Results Methylation of ASC gene was not observed in eilher normal ovarian tissues or benign ovarian tumors, while the methylated ratio of ASC in ovarian caner was 38.9 % （7/18）. The mRNA and protein expression of ASC was decreased gradually among the normal ovarian tissues, benige ovarian tumors and ovarian cancers. Moreover, the ASC expression was more down-regulated in methylated ovarian cancers than that in un methylated specimens. The expression of ASC in high moderately differentiated ovarian cancers was higher than that in low differentiated ovarian cancers. Conclusion Melhylation of ASC is one of an important mechanisms for the loss of expression of this gene. Aberrant methylation of ASC may play a role in the pathogenesis of ovarian cancer.