乳腺癌中RIZ1基因启动子甲基化状态的探讨
Methylation of the RIZ1 Promoter in Breast Cancer
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摘要: 目的:研究乳腺癌组织中RIZ1启动子甲基化状态及与临床、病理指标之间的关系,并探讨该甲基化状态与RIZ1 mRNA表达的相关性。方法:应用甲基化特异性PCR法(methylation specific PCR,MSP)检测人乳腺癌组织和相应癌旁组织及乳腺良性肿瘤组织中RIZ1启动子甲基化状态,结合患者的临床与病理资料分析结果,并结合半定量RT-PCR法检测结果加以分析。结果:34例乳腺癌标本中RIZ1启动子甲基化阳性率为44.1%(15/34),该甲基化状态与患者年龄、肿瘤TNM分期、有无淋巴结转移、雌激素受体(ER)是否阳性无相关性(均为P>0.05)。RIZ1启动子甲基化标本中的RIZ1 mRNA表达水平低于未甲基化标本者,两者差异具有显著性(P<0.05),RIZ1表达降低与其启动子高甲基化状态之间有相关性(P<0.05)。结论:RIZ1基因启动子高甲基化是乳腺癌中常见的分子病理学改变之一;RIZ1 mRNA表达与RIZ1启动子高甲基化呈负相关。Abstract: Objective: To investigate methylation of the RIZ1 promoter in human breast cancer tissue and its significance in related clinical and pathological data, and to explore its relationship to RIZ1 mRNA expression. Methods: Methylation-specific PCR(MSP) was performed to detect the methylation status of the RIZ1 promoter in human breast paraneoplastic tissue specimens and in benign breast tumor tissue specimens. The results were analyzed in combination with the clinical and pathological data of the patients and the RT-PCR results. Results: Among the 34 breast cancer specimens,RIZ1 promoter methylation was detected in 15 cases (44.1%). No relationship has been found between RIZ1 promoter methylation and clinical parameters including age, TNM stages, lymph node metastasis or ER status (P>0.05 for each parameter). The expression of RIZ1 mRNA was found to be lower in the specimens with RIZ1 promoter methylation than in those specimens with promoters that were unmethylated (P<0.05). Downregulated RIZ1 expression had a correlation with hypermethylation of the promoter (P<0.05). Conclusion: Hypermethylation of the RIZ1 promoter is a frequent molecular pathological event in breast cancer. RIZ1 mRNA expression is downregulated when the promoter is hypermethylated.