MAGE-A1 和-A3 启动子甲基化和 DNA 甲基转移酶表达在喉鳞状细胞癌患者中的临床意义。

The clinical significance of methylation of MAGE-A1 and-A3 promoters and expression of DNA methyltransferase in patients with laryngeal squamous cell carcinoma.

机构信息

Department of Otolaryngology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China; Department of Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.

Department of Otolaryngology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.

出版信息

Am J Otolaryngol. 2020 Jan-Feb;41(1):102318. doi: 10.1016/j.amjoto.2019.102318. Epub 2019 Oct 18.

DOI:10.1016/j.amjoto.2019.102318

PMID:31732299

Abstract

PURPOSE

Abnormal DNA methylation plays an important role in clinical diagnosis and prognosis of various tumors. DNA methylation is catalyzed by DNA methyltransferase (DNMT). However, the methylation status of MAGE-A1 and MAGE-A3 promoter regions in LSCC is unclear. To investigate the methylation levels of MAGE-A1, -A3 in LSCC and corresponding normal tissues. The expression of DNMTs (DNMT1, DNMT3a and DNMT3b) in LSCC and the relationship between the methylation status of MAGE-A1, -A3 were analyzed.

MATERIALS AND METHODS

We examined methylation status of MAGE-A1, -A3 in LSCC by using MSP. Meanwhile, the expression level of DNMTs in LSCC was detected by immunohistochemistry. And further analysis the correlation between DNMTs expression level and methylation status of MAGE-A1 and MAGE-A3.

RESULTS

The unmethylation rate of MAGE-A1, -A3 were 39.62% and 46.23%. The expression of DNMTs was 33.02% to 37.74%. The level of demethylation of MAGE-A1 and MAGE-A3 were negative related to DNMTs protein. MAGE-A1 and MAGE-A3 unmethylation status and DNMT3a expression were independent prognostic factors for LSCC.

CONCLUSIONS

The DNMTs may participate in the methylation process of MAGE-A1 and MAGE-A3, which may play an important role in the occurrence and development of LSCC.

摘要

目的

异常的 DNA 甲基化在各种肿瘤的临床诊断和预后中起着重要作用。DNA 甲基化由 DNA 甲基转移酶（DNMT）催化。然而，LSCC 中 MAGE-A1 和 MAGE-A3 启动子区域的甲基化状态尚不清楚。本研究旨在检测 LSCC 及相应正常组织中 MAGE-A1、-A3 的甲基化水平。分析 LSCC 中 DNMTs（DNMT1、DNMT3a 和 DNMT3b）的表达情况，以及 MAGE-A1、-A3 甲基化状态之间的关系。

材料和方法

采用 MSP 检测 LSCC 中 MAGE-A1、-A3 的甲基化状态，同时采用免疫组织化学法检测 LSCC 中 DNMTs 的表达水平，并进一步分析 DNMTs 表达水平与 MAGE-A1 和 MAGE-A3 甲基化状态之间的相关性。

结果

MAGE-A1、-A3 的非甲基化率分别为 39.62%和 46.23%，DNMTs 的表达率为 33.02%至 37.74%。MAGE-A1 和 MAGE-A3 的去甲基化水平与 DNMTs 蛋白呈负相关。MAGE-A1 和 MAGE-A3 的非甲基化状态和 DNMT3a 的表达是 LSCC 的独立预后因素。