Caveolin-1基因的甲基化状态与食管胃结合部腺癌中Caveolin-1 mRNA,Caveolin-1蛋白及Her-2蛋白表达的相关性

Correlation between methylation of Caveolin-1 and expression of Caveolin-1 mRNA, Caveolin-1 protein and Her-2 protein in human adenocarcinomas of the esophagogastric junction

目的:检测食管胃结合部腺癌(adenocarcinomas of the esophagogastric junction,AEG)及远端正常组织(距癌灶>10 cm)中Caveolin-1的甲基化水平,研究该基因甲基化对其mRNA、蛋白质及人类表皮生长因子受体2(human epidermal growth factor receptor-2,Her-2)蛋白在AEG中表达的相关性。方法:采用甲基化特异性PCR(methylation-specific PCR,MSP)法检测67例食管胃结合部腺癌及远端正常组织中Caveolin-1的甲基化状态;采用RT-PCR法检测食管胃结合部腺癌及远端正常组织中Caveolin-1 mRNA表达情况;应用免疫组织化学法检测Caveolin-1蛋白及Her-2蛋白的表达情况;进一步分析Caveolin-1的甲基化状态与其mRNA、蛋白及Her-2蛋白的表达的相关性。结果:在食管胃结合部腺癌中,Caveolin-1的甲基化表达率为28.4%(19/67),远端正常组织中未发现该基因的甲基化现象,差异有统计学意义(P<0.01);癌组织中Caveolin-1的甲基化水平与患者的肿瘤大小、分化程度及淋巴结转移方面有关,差异有统计学意义(P<0.05);而与性别、年龄、有无脉管癌栓及临床分期无关,差异无统计学意义(P>0.05);癌组织中Caveolin-1 mRNA及蛋白的阳性表达率分别为46.3%和41.8%,均明显低于远端正常组织,差异有统计学意义(P<0.01)。癌组织中Caveolin-1蛋白及Her-2蛋白的阳性表达率分别为41.8%和56.7%,均与Caveolin-1的甲基化状态相关,差异有统计学意义(P<0.05)。结论:Caveolin-1甲基化可能参与了肿瘤的表达,并且Caveolin-1甲基化可能与食管胃结合部腺癌中Caveolin-1 mRNA,Caveolin-1蛋白及Her-2蛋白的表达相关,在食管胃结合部腺癌的发生及发展中发挥着重要的作用。

Objective:To investigate the methylation level of Caveolin-1 in human adenocarcinomas of the esophagogastric junction(AEG)and the distal normal tissue from carcinoma(>10 cm),and to study the expression of Caveolin-1 mRNA,Caveolin-1 protein and Her-2 protein in AEG and their relationships with the methylation of Caveolin-1.Methods:Methylation-specific PCR(MSP)method was used to detect the methylation status of Caveolin-1 in 67 patients with AEG and distal normal tissue from carcinoma;the expression of Caveolin-1 mRNA was detected in AEG and the distal normal tissue from carcinoma by RT-PCR;the expression of Caveolin-1 protein and Her-2 protein was detected by immunohistochemical method;the correlation between the methylation of Caveolin-1 and the expression of Caveolin-1 mRNA,Caveolin-1 protein and Her-2 protein was further analyzed.Results:Methylation of Caveolin-1 was expressed as 28.4%(19/67)in AEG,and no methylation of this gene was found in the distal normal tissue from carcinoma,and the difference was statistically significant(P<0.01).Methylation level of Caveolin-1 in carcinoma tissues was related to tumor size,differentiated degree and lymph node metastasis of patients,and the difference was statistically significant(P<0.05),but there was not related to gender,age,presence of vascular carcinoma thrombus and clinical stages,and the difference was not statistically significant(P>0.05).The positive expression rate of Caveolin-1 mRNA and the protein in carcinoma tissues were 46.3%and 41.8%,which were both lower than the expression rate of that in the distal normal tissue from carcinoma,and the difference was statistically significant(P<0.01).The positive expression rate of Caveolin-1 protein and Her-2 protein in carcinoma tissues were 41.8%and 56.7%,which both related to the methylation state of Caveolin-1,and the difference was statistically significant(P<0.05).Conclusion:Methylation of Caveolin-1 may be involved in the expression of carcinoma,and may be associated with the expression of Caveolin-1 mRNA,Caveolin-1 protein and Her-2 protein in AEG,which may play an important role in the occurrence and development of AEG.