上皮性卵巢癌RASSF2A基因甲基化及其表达的临床意义

发布时间：2018-01-19 18:17

本文关键词： 上皮性卵巢癌甲基化 RAS相关结构域蛋白A基因基因检测　出处：《中华肿瘤防治杂志》2015年20期 　论文类型：期刊论文

【摘要】：目的 RAS相关结构域蛋白1A基因(RAS associated domain family 1Agene,RASSF1A)启动子区超甲基化介导的基因转录失活在卵巢癌中频见,可作为卵巢癌诊治过程中有意义的分子生物学指标,RAS相关结构域蛋白2A基因(RAS associated domain family 2Agene,RASSF2A)与RASSF1A同源,其基因异常甲基化在多种肿瘤发生发展中发挥重要作用。本研究探讨上皮性卵巢癌组织RASSF2A甲基化水平,并分析其临床意义及高甲基化与mRNA表达情况的相关性。方法选择2013-10-01-2014-12-31聊城市人民医院手术治疗的50例上皮性卵巢癌、27例交界性上皮性卵巢肿瘤和20例良性上皮性卵巢肿瘤患者,应用甲基化特异性PCR(MSP)检测卵巢肿瘤组织中RASSF2A基因启动子甲基化状态,采用RT-PCR检测其mRNA表达水平。采用5-氮杂2′-脱氧胞苷(5-aza-dC)对人卵巢癌细胞株SKOV3、3AO进行去甲基化干预实验,并检测药物作用前后RASSF2A基因启动子甲基化及其mRNA的表达情况。结果 RASSF2A基因mRNA在良性上皮性卵巢肿瘤中的表达阳性率为95.00%(19/20),交界性上皮性卵巢肿瘤为59.26%(16/27),上皮性卵巢癌组织为34.00%(17/50),表达强度依次下降,差异有统计学意义,χ2=21.855,P0.001。RASSF2A基因启动子在良性上皮性卵巢肿瘤组织中的甲基化率为0(0/20),交界性上皮性卵巢肿瘤为22.22%(6/27),上皮性卵巢癌组织为46.00%(23/50),差异有统计学意义,χ2=15.474,P0.001。RASSF2A甲基化水平与卵巢癌患者的年龄、病理类型、临床分期、组织分化程度及淋巴结转移无明显相关性。RASSF2A基因甲基化与其mRNA的表达呈负相关,甲基化阳性组织的mRNA表达水平明显低于甲基化阴性组织。5-aza-dC药物作用后,卵巢癌细胞株中RASSF2A基因甲基化被逆转,而其基因表达明显升高。结论 RASSF2A启动子区高甲基化导致的基因表达沉默与上皮性卵巢癌的发生发展有关。
[Abstract]:Objective to study the RAS associated domain protein 1A gene, Ras associated domain family 1Agene. The transcriptional inactivation of genes mediated by hypermethylation in the promoter region of RASSF1A can be regarded as a significant molecular biological marker in the diagnosis and treatment of ovarian cancer. The RAS related domain protein 2A gene (Ras associated domain family 2AgeneA) is homologous to RASSF1A. Aberrant methylation plays an important role in the carcinogenesis and development of epithelial ovarian cancer. This study was designed to investigate the level of RASSF2A methylation in epithelial ovarian cancer tissues. The clinical significance of hypermethylation and the correlation between hypermethylation and mRNA expression were analyzed. Methods 50 cases of epithelial epithelium treated by operation in Liaocheng people's Hospital 2013-10-01-2014-12-31 were selected. Ovarian cancer. There were 27 borderline epithelial ovarian tumors and 20 benign epithelial ovarian tumors. The methylation status of RASSF2A promoter in ovarian tumor tissues was detected by methylation-specific PCR. The expression level of mRNA was detected by RT-PCR, and 5-aza-dC (5-aza-dC) was used to detect the expression of SKOV3 in human ovarian cancer cell line. 3The intervention experiment of demethylation was carried out by AO. The methylation of RASSF2A gene promoter and the expression of mRNA were detected before and after drug treatment. The positive rate of RASSF2A mRNA expression in benign epithelial ovarian tumors was 95.00. 19 / 20. The number of borderline epithelial ovarian tumors was 59.26 / 27 and that of epithelial ovarian carcinomas was 34.00 / 50. The intensity of expression decreased in turn with statistical significance. The methylation rate of the promoter of RASSF2A gene in benign epithelial ovarian tumors was 0 / 20). The number of borderline epithelial ovarian tumors was 22.22 / 27, and that of epithelial ovarian cancer was 46.00 / 50, the difference was statistically significant (蠂 ~ 2 / 15.474). P0.001. RASSF2A methylation level was associated with age, pathological type, and clinical stage of patients with ovarian cancer. There was no significant correlation between tissue differentiation and lymph node metastasis. The methylation of RASSF2A gene was negatively correlated with the expression of mRNA. The level of mRNA expression in methylated positive tissue was significantly lower than that in methylated negative tissue. 5-aza-dC could reverse the methylation of RASSF2A gene in ovarian cancer cell line. Conclusion the silencing of gene expression induced by hypermethylation of RASSF2A promoter is related to the occurrence and development of epithelial ovarian cancer.
【作者单位】：聊城市人民医院妇产科;聊城市东昌府人民医院妇产科;
【分类号】：R737.31
【正文快照】： 中华肿瘤防治杂志,2015,22(20):1609-1613Chin J Cancer Prev Treat,2015,22(20):1609-1613上皮性卵巢癌是女性生殖系统中恶性程度最高和预后最差的肿瘤,其病死率居妇科恶性肿瘤首位[1]。大量研究已证实,RAS相关结构域蛋白1A基因(RAS associated domain family 1Agene,RASSF1A

【相似文献】