Methylation of RASSF1A gene promoter and the correlation with DNMT1 expression that may contribute to esophageal squamous cell carcinoma.
Methylation of RASSF1A gene promoter and the correlation with DNMT1 expression that may contribute to esophageal squamous cell carcinoma.
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RASSF1A基因启动子甲基化及其与DNMT1表达的相关性可能与食管鳞癌有关
DOI：
10.1186/s12957-015-0557-y
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发表时间：
2015-04-08
影响因子：
3.2
通讯作者：
Song J
中科院分区：
文献类型：
--
作者：
Du Z;Ma K;Sun X;Li A;Wang H;Zhang L;Lin F;Feng X;Song J
食管鳞状细胞癌是世界上最常见的恶性肿瘤之一。研究证实，食管鳞状细胞癌中存在许多基因异常高甲基化。目的是检测食管癌组织中RASSF1A基因启动子的甲基化和DNA甲基转移酶1 （DNMT1）蛋白的表达，并探讨它们与食管鳞状细胞癌的关系。分析了100例肿瘤标本及其邻近组织中RASSF1A基因的CpG岛甲基化状态，用于甲基化特异性聚合酶链反应（MSP）。免疫组化法检测DNMT1蛋白表达。通过t检验和卡方检验比较计量资料与分类资料的差异。所有的统计数据都是通过双边检验得出的。差异有统计学意义（P < 0.05）。100例食管鳞癌中有45例（45%）检测到RASSF1A基因启动子甲基化，而100例邻近正常组织中有2例（2%）检测到RASSF1A基因甲基化。RASSF1A基因启动子在癌组织中高度甲基化，在正常食管组织和食管鳞癌中差异有统计学意义（P < 0.05）。100例（61%）食管鳞癌中有61例检测到DNMT1蛋白的表达，其中上述45例RASSF1A基因启动子甲基化样本中有41例，邻近组织中无DNMT1蛋白表达。DNMT1蛋白在癌组织中高表达，差异有统计学意义（P < 0.05）。在RASSF1A甲基化阳性病例中，45例中有41例（91%）检测到DNMT1蛋白，而在55例非甲基化癌症病例中，有20例（36.3%）检测到DNMT1蛋白，差异有统计学意义（P < 0.05）。食管鳞状癌的发生可能与DNMT1和RASSF1A启动子CpG岛的高甲基化有关，因为它们的高表达和高甲基化。
Esophageal squamous cell carcinoma is one of the most common malignancies in the world. Studies have confirmed that there are many genes abnormally hypermethylated in esophageal squamous cell carcinoma. The objective is to detect methylation of the RASSF1A gene promoter and the expression of the DNA methyltransferase 1 (DNMT1) protein in esophageal cancer tissue and discuss their relationship with esophageal squamous cell carcinoma. The CpG island methylation status of RASSF1A genes were analyzed in 100 cases of tumor specimens as well as their adjacent tissues which was used for methylation-specific polymerase chain reaction (MSP). The expression of DNMT1 protein was determined by immunohistochemistry. Difference between measurement data and categorical data was compared through analysis of t test and chi-square test. All the statistics were taken with a bilateral test. The difference was statistically significant (P < 0.05). The promoter methylation of the RASSF1A gene promoter has been detected in 45 out of 100 (45%) esophageal squamous carcinoma cases, while methylation of RASSF1A gene has been detected in 2 out of 100 adjacent normal tissues (2%). The RASSF1A gene promoter was highly methylated in cancer tissues, and there were significant differences between normal esophagus tissues and esophageal squamous carcinoma (P < 0.05). The expression of DNMT1 protein has been detected in 61 out of 100 (61%) esophageal squamous carcinoma cases, including 41 cases in the above 45 methylated samples of RASSF1A gene promoter, and none in adjacent tissues. DNMT1 proteins are highly expressed in cancer tissues, and there were significant differences (P < 0.05). In positive cases for methylation of RASSF1A, the DNMT1 protein had been detected in 41 out of 45 (91%), while in non-methylated cancer cases, 20 out of 55(36.3%), and the difference is significant (P < 0.05). Esophageal squamous carcinoma tumorigenesis may be related with hypermethylation of DNMT1 and RASSF1A promoter CpG island due to their high expression and also their hypermethylation.
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