Aberrant methylation of CDH13 gene in nasopharyngeal carcinoma could serve as a potential diagnostic biomarker
Aberrant methylation of CDH13 gene in nasopharyngeal carcinoma could serve as a potential diagnostic biomarker
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DOI：
10.1016/j.oraloncology.2006.01.007
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发表时间：
2007-01-01
期刊：
影响因子：
4.8
通讯作者：
Hu, Lifu
中科院分区：
文献类型：
--
作者：
Sun, Di;Zhang, Zhe;Hu, Lifu
CDH 13编码细胞粘附分子H-钙粘蛋白。在这项研究中，我们研究了CDH 13甲基化在鼻咽癌（NPC）。甲基化特异性PCR检测结果显示，20%（1/5）的鼻咽癌细胞系、100%（2/2）的鼻咽癌移植瘤和89.7%（52/58）的鼻咽癌原发瘤中CDH 13基因甲基化，而正常鼻咽上皮中仅10%（1/10）甲基化（P < 0.05）。RT-PCR分析CDH 13在鼻咽癌细胞系和移植瘤中的表达，结果显示CDH 13的表达与其甲基化状态呈负相关。在CDH 13沉默的细胞系中，去甲基化剂5-氮杂脱氧胞苷可以显着恢复CDH 13的表达。综上所述，CDH 13基因启动子在鼻咽癌组织中存在异常甲基化，启动子甲基化在H-cadherin表达沉默中起着关键作用。此外，从鼻咽拭子检测CDH 13甲基化的高灵敏度（81%）和特异性（0%假阳性）表明其可用作早期诊断的工具。(c)2006爱思唯尔有限公司保留所有权利。
CDH13 encodes a cell adhesion molecule, H-cadherin. In this study, we examined CDH13 methylation in nasopharyngeal carcinoma (NPC). Methylation specific PCR results showed that CDH13 was methylated in 20% (1/5) NPC cell lines, 100% (2/2) NPC xenografts and 89.7% (52/58) of the NPC primary tumors, while only methylated in 10% (1/10) normal nasopharyngeal epithelia (P < 0.05). CDH13 expression in NPC cell lines and NPC xenografts analyzed by RT-PCR showed that expressions of CDH13 were reversely correlated with their methylation status. In CDH13-silenced cell line, demethylating agent 5-aza-deoxycytidine could dramatically restore CDH13 expression. Taken together, CDH13 promoter is aberrantly methylated in NPC both in vitro and in vivo, and promoter methylation plays a pivotal role in the silencing of H-cadherin expression. Furthermore, the high sensitivity (81%) and specificity (0% false positives) of detecting CDH13 methylation from nasopharyngeal swabs suggest it could be utilized as a tool for early diagnosis. (c) 2006 Elsevier Ltd. All rights reserved.