Hypermethylation of epithelial-cadherin gene promoter is associated with Epstein-Barr virus in nasopharyngeal carcinoma
Hypermethylation of epithelial-cadherin gene promoter is associated with Epstein-Barr virus in nasopharyngeal carcinoma
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DOI：
10.1016/j.cdp.2008.05.005
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发表时间：
2008-01-01
影响因子：
--
通讯作者：
Leopairat, Juvady
中科院分区：
文献类型：
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作者：
Niemhom, Sopaporn;Kitazawa, Sohei;Leopairat, Juvady
背景资料：EB病毒（Epstein-Barr virus，EBV）是鼻咽癌（nasopharyngeal carcinoma，NPC）的重要病原体，但其发生、发展及致病机制尚不清楚。EB病毒LMP 1可通过DNA甲基转移酶激活鼻咽癌细胞系上皮钙粘蛋白（E-cadherin）启动子的超甲基化。通过对鼻咽癌组织中EB病毒基因组和E-cadherin基因启动子甲基化的研究，探讨EB病毒在鼻咽癌发病机制中的作用。研究方法：应用甲基化特异性聚合酶链反应（MSP）检测鼻咽癌石蜡包埋组织和正常鼻咽组织中E-钙粘蛋白基因启动子区的甲基化。用PCR方法检测组织标本中的EBV基因组。结果如下：与鳞状细胞癌相比，未分化和非角化型NPC中E-cadherin启动子和EBV的高甲基化更明显。在38例患者样本中，有28例（73.7%）发现E-钙粘蛋白高甲基化。在28例鼻咽癌标本中，22例（78.6%）检出EB病毒，表现为E-钙粘蛋白高甲基化。正常鼻咽组织中未检测到EBV基因组和甲基化。在E-钙粘蛋白高甲基化和EBV基因组之间发现了显著关联（p < 0.001; Fisher精确检验）。与早期NPC相比，晚期NPC中E-钙粘蛋白的高甲基化更常见（p = 0.036; Fisher精确检验）。结论：EBV的高发病率与E-cadherin高甲基化的一致性，特别是在未分化和非角化型NPC中，提示EBV在高甲基化中的作用。EBV存在于鼻咽癌的早期，可诱导鼻咽癌细胞的甲基化，并促进鼻咽癌向晚期发展。(C)2008年国际预防肿瘤学会。由爱思唯尔有限公司出版。保留所有权利。
Background: Epstein-Barr virus (EBV) is documented as the important etiologic agent of nasopharyngeal carcinoma (NPC) but the mechanism of development and pathogenesis induced by EBV is presently unclear. Hypermethylation of epithelial-cadherin (E-cadherin) promoter has been shown to be induced in NPC cell line by EBV LMP1 via DNA methyltransferase activation. EBV genomes and hypermethylation of E-cadherin promoter were investigated in NPC tissues to evaluate the role of EBV in the hypermethylation and pathogenesis of NPC. Methods: Methylation-specific polymerase chain reaction (MSP) was performed to detect E-cadherin promoter hypermethylation in paraffin embedded tissues from patients with NPC and normal nasopharyngeal tissues. EBV genomes were detected by PCR in the tissue samples. Results: Hypermethylation of E-cadherin promoter and EBV were predominantly detected in undifferentiated and non-keratinizing NPC compared to those in squamous cell NPC. Hypermethylation of E-cadherin was found in 28 of 38 (73.7%) patient samples. EBV was detected in 22 of the 28 (78.6%) NPC samples demonstrating E-cadherin hypermethylation. EBV genomes and hypermethylation were not detected in normal nasopharyngeal tissues. Significant association was found between E-cadherin hypermethylation and EBV genomes (p < 0.001; Fisher's exact test). Hypermethylation of E-cadherin was more frequently detected in advanced stages compared to those in early stages of NPC (p = 0.036; Fisher's exact test). Conclusions: The high incidence of EBV with the consistency of E-cadherin hypermethylation, particularly in undifferentiated and non-keratinizing NPC suggests the role of EBV in the hypermethylation. EBV exists at early stage of NPC that induces the hypermethylation and contributes to progression of the disease to the advanced stage of NPC. (C) 2008 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved.