文章摘要

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

作者: 1石 晓鹏, 1尹 颖, 1张 金平, 1孔 易
1 武安市第一人民医院病理科,河北 武安 056300
通讯: 孔 易 Email: kongyi1111@163.com
DOI: 10.3978/j.issn.2095-6959.2020.02.004
基金: 河北省卫生厅研究与发展项目(20171168)。

摘要

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。
关键词: 食管胃结合部腺癌;Caveolin-1甲基化;Caveolin-1蛋白;Her-2蛋白

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

Authors: 1SHI Xiaopeng, 1YIN Ying, 1ZHANG Jinping, 1KONG Yi
1 Department of Pathology, Wu’an No. 1 People’s Hospital, Wu’an Hebei 056300, China

CorrespondingAuthor:KONG Yi Email: kongyi1111@163.com

Foundation: This work was supported by Research and Development Project, Health Commission of Hebei Province,China (20171168)

Abstract

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.
Keywords: adenocarcinomas of the esophagogastric junction; methylation of Caveolin-1; Caveolin-1 protein; Her-2 protein