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目的:研究乳腺癌组织中死亡相关蛋白激酶(death-associated protein kinase 1,DAPK1)启动子甲基化状态及其与临床病理特征之间的关系,并探讨该甲基化状态与DAPK1 mRNA表达的相关性。方法:应用甲基化特异性PCR法检测人乳腺癌组织和相应癌旁正常乳腺组织中DAPK1启动子甲基化状态,分析其与患者临床病理特征的关系,并结合半定量RT-PCR法的检测结果加以分析。结果:43例乳腺癌标本中DAPK1启动子甲基化阳性率为44.1%(20/43),DAPK1启动子甲基化状态与年龄、肿瘤大小、组织学分级、TNM分期、ER状态、PR状态、Her2状态无关(P>0.05),而与有无淋巴结转移、P53是否阳性有关(P<0.05)。DAPK1启动子甲基化标本中的DAPK1mRNA表达水平低于未甲基化标本,两者差异具有统计学意义(P<0.05)。结论:乳腺癌中DAPK1基因启动子区高甲基化与其mRNA失表达有关,在乳腺癌发生、发展中可能起重要作用,有可能作为乳腺癌诊断和预后分析的检测指标之一。
OBJECTIVE: To investigate the relationship between the methylation status of death-associated protein kinase 1 (DAPK1) promoter and clinicopathological features in breast cancer and to investigate the relationship between methylation status and DAPK1 mRNA expression Correlation. Methods: Methylation-specific PCR was used to detect the methylation status of DAPK1 promoter in human breast cancer tissues and corresponding normal breast tissues. The relationship between DAPK1 promoter methylation status and clinicopathological features was analyzed. Combined with semi-quantitative RT-PCR Test results to be analyzed. Results: The positive rate of DAPK1 promoter methylation was 44.1% (20/43) in 43 cases of breast cancer specimens. The methylation status of DAPK1 promoter was related to age, tumor size, histological grade, TNM stage, ER status and PR status , Her2 status (P> 0.05), but with or without lymph node metastasis, P53 is positive (P <0.05). The level of DAPK1 mRNA in DAPK1 promoter methylation was lower than that in non-methylation samples (P <0.05). Conclusion: The hypermethylation of DAPK1 promoter in breast cancer is related to the loss of expression of DAPK1 gene, which may play an important role in the occurrence and development of breast cancer. It may be used as one of the detection indexes for the diagnosis and prognosis of breast cancer.