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目的:探讨RASSF1A基因的异常表达与食管鳞癌(esophageal squamous cell carcinoma,ESCC)发生发展的关系.方法:应用实时RT-PCR方法及实时荧光甲基化特异性聚合酶链反应技术,分别检测49例ESCC患者癌组织及癌旁正常组织中RASSF1A基因的转录表达情况和启动子区域5’-CpG岛的甲基化状态.分析RASSF1A基因在ESCC中的转录表达情况、甲基化状态及与临床病理因素、预后之间的关系.结果:在49例ESCC标本中,有26(53.06%)例RASSF1A mRNA表达下调,RASSF1A mRNA在食管鳞癌组织及相应的癌旁正常组织中的表达存在显著统计学差异(P<0.05),RASSF1A mRNA的表达缺失与ESCC患者的淋巴结转移、临床TNM分期及不良预后均存在显著相关性(均P<0.05);有38(77.60%)例RASSF1A基因启动子区域5’-CpG岛高甲基化,与之相对应的癌旁正常组织中仅有3(6.10%)例,两者差异有统计学意义(P<0.05),RASSF1A基因的高甲基化状态与淋巴结转移、临床TNM分期及不良预后均存在显著相关性(均P<0.05);在26例RASSF1A基因转录表达缺失的ESCC组织中有24例发生了启动子区域5’-CpG岛的高甲基化,RASSF1A基因在ESCC中的转录表达缺失与其启动子5’-CpG岛高甲基化显著相关(P<0.05).结论:RASSF1A基因启动子5’-CpG岛高甲基化在ESCC是一高频分子事件,与该基因的转录表达缺失显著相关,是其转录表达缺失的主要机制之一.
Objective: To investigate the relationship between the abnormal expression of RASSF1A gene and the development of esophageal squamous cell carcinoma (ESCC). Methods: Real-time RT-PCR method and real-time fluorescence methylation-specific polymerase chain reaction technique were used to detect 49 The transcriptional expression of RASSF1A gene and the methylation status of the 5′-CpG island in the promoter region in cancer tissue and adjacent normal tissues of ESCC patients. Analysis of transcript expression status, methylation status, and clinical status of RASSF1A gene in ESCC The relationship between pathological factors and prognosis. Results: In 49 ESCC specimens, there were 26 (53.06%) cases of RASSF1A mRNA down-regulation, RASSF1A mRNA expression in esophageal squamous cell carcinoma tissue and corresponding adjacent normal tissue has significant statistics. Differences in learning (P<0.05). Loss of RASSF1A mRNA expression was significantly associated with lymph node metastasis, clinical TNM staging, and poor prognosis in ESCC patients (all P<0.05); there were 38 (77.60%) cases of RASSF1A gene promoter regions. The hypermethylation of 5’-CpG islands was associated with only 3 (6.10%) of the normal tissue adjacent to the tumor. There was a statistically significant difference between the two (P<0.05), the hypermethylation status of RASSF1A gene and lymph node metastasis, Clinical TNM There was a significant correlation between stage and poor prognosis (all P<0.05). Hypermethylation of the 5′-CpG island in the promoter region was found in 24 of the 26 ESCC tissues with loss of RASSF1A gene expression. The RASSF1A gene was in ESCC. The lack of transcriptional expression was significantly associated with hypermethylation of its promoter 5′-CpG island (P<0.05). Conclusion: Hypermethylation of the RASSF1A gene promoter 5′-CpG island is a high-frequency molecular event in ESCC, and its transcriptional expression Deletion is significantly related to one of the major mechanisms of the loss of its transcriptional expression.