The first 2 authors contributed equally to this work.
Endoglin promoter hypermethylation identifies a field defect in human primary esophageal cancer
Article first published online: 24 JUL 2013
Copyright © 2013 American Cancer Society
Volume 119, Issue 20, pages 3604–3609, 15 October 2013
How to Cite
Jin, Z., Zhao, Z., Cheng, Y., Dong, M., Zhang, X., Wang, L., Fan, X., Feng, X., Mori, Y. and Meltzer, S. J. (2013), Endoglin promoter hypermethylation identifies a field defect in human primary esophageal cancer. Cancer, 119: 3604–3609. doi: 10.1002/cncr.28276
- Issue published online: 4 OCT 2013
- Article first published online: 24 JUL 2013
- Manuscript Accepted: 13 MAY 2013
- Manuscript Revised: 6 MAY 2013
- Manuscript Received: 5 MAR 2013
- esophageal adenocarcinoma;
- esophageal squamous cell carcinoma;
Endoglin (ENG) is a 180-kilodalton transmembrane glycoprotein that functions as a component of the transforming growth factor-β receptor complex. Recently, ENG promoter hypermethylation was reported in several human cancers.
The authors examined ENG promoter hypermethylation using real-time, quantitative, methylation-specific polymerase chain reaction in 260 human esophageal tissues.
ENG hypermethylation demonstrated highly discriminative receiver operating characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) from normal esophagus (P < .01). It is interesting to note that ENG normalized methylation values were significantly higher in ESCC compared with normal tissue (P < .01) or EAC (P < .01). The ENG hypermethylation frequency was 46.2% in ESCC and 11.9% in normal esophageal tissue, but increased early and sequentially during EAC-associated neoplastic progression to 13.3% in Barrett metaplasia (BE), 25% in dysplastic BE, and 26.9% in frank EAC. ENG hypermethylation was significantly higher in normal esophageal tissue from patients with ESCC (mean, 0.0186) than in normal tissue from patients with EAC (mean, 0.0117; P < .05). Treatment of KYSE220 ESCC cells with the demethylating agent 5-aza-2′-deoxycytidine was found to reverse ENG methylation and reactivate ENG mRNA expression.
Promoter hypermethylation of ENG appears to be a frequent, tissue-specific event in human ESCC and exhibits a field defect with promising biomarker potential for the early detection of ESCC. In addition, ENG hypermethylation occurs in a subset of human EAC, and early during BE-associated esophageal neoplastic progression. Cancer 2013;119:3604–3609. © 2013 American Cancer Society.