RASSF 1A基因在卵巢癌组织及腹腔冲洗液中甲基化的研究

摘要

Objective:To investigate the promoter hypermethylation status of tumor suppressor Ras association domain family 1A ( RASSF 1 A) gene in ovarian cancer, peritoneal fluid and the value of diagnosis of ovarian cancer. Methods: The promoter methylation status of the promoter region of RASSF 1A was analyzed by methylation specific-PCR in forty-two malignant ovarian tumor tissues and ascites( or peritoneal fluid) ,eleven normal ovarian tissues and ninteen benign ovarian tumor tissues. Results:The promoter methylation rate of RASSF 1A in ovarian cancer was 38.1％ while in benign tissues was 0. The rate of promoter hypermethylation of RASSF 1 A in ovarian cancer and noncancer tissues showed significant correlation( P ＜ 0. 01 ). The frequency of promoter methylation of RASSF 1A was correlated with operation-pathology stage and lymph node metastasis. There was statistically significant difference. Hypermethylation of RASSF 1A gene happened more often in tumors in stage Ⅲ and Ⅳ 54.2％ than that in stage Ⅰ and Ⅱ 16.6％ (P ＜0.05). The frequency of promoter methylation of RASSF 1A was significantly higher in the patients with positive lymph node metastasis 56.5％ than those without lymph node metastasis 15.8％ (P ＜0. 01 ). The frequency of methylation of promoter region in RASSF 1A gene was significantly higher in the patients with positive ascites or peritoneal liquid 74.1％ than in those negative ascites or peritoneal liquid 33.3％ (P ＜0. 01 ). Conclusions:There was significant frequency promoter methylation of RASSF 1A in ovarian cancer. Detection of aberrant RASSF 1A methylation may serve as an early diagnostic and prognostic marker.%目的:探讨卵巢癌组织和腹腔冲洗液中Ras相关区域家族1A(Ras association domain family 1A,RASSF 1A)基因启动子异常甲基化状况及其在卵巢癌诊断中的价值.方法:采用甲基化特异性PCR方法检测42例卵巢癌组织、腹腔冲洗液或腹腔积液、11例正常卵巢组织和19例良性病变卵巢组织中RASSF 1A基因启动子区甲基化状态.结果:42例卵巢癌组织中RASSF 1A基因启动子区甲基化发生率为38.1%,11例正常卵巢组织和19例良性卵巢组织中RASSF 1A基因启动子区无甲基化,差异有统计学意义(P<0.01).临床分期Ⅲ期和Ⅳ期的卵巢癌组织中RASSF 1A基因启动子区甲基化发生率为54.2%,高于临床Ⅰ期和Ⅱ期者16.6%(P<0.05).淋巴结阳性者癌组织中RASSF 1A基因启动子区甲基化发生率56.5%,高于淋巴结阴性者15.8%.腹腔冲洗液或腹腔积液细胞学阳性者癌组织中RASSF 1A基因启动子区甲基化发生率为74.1%,高于腹腔冲洗液或腹腔积液细胞学阴性者33.3%(P<0.01).结论:RASSF 1A基因甲基化在卵巢癌患者中具有较高的发生率,检测卵巢癌组织和腹腔冲洗液或腹腔积液中RASSF 1A基因的甲基化状态对卵巢癌的诊断和判断预后具有一定的价值.