Endoglin promoter hypermethylation identifies a field defect in human primary esophageal cancer.
Endoglin promoter hypermethylation identifies a field defect in human primary esophageal cancer.
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内皮糖蛋白启动子高甲基化鉴定了人类原发性食管癌的场缺陷
DOI:
10.1002/cncr.28276
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发表时间:
2013-10-15
期刊:
影响因子:
6.2
通讯作者:
Meltzer, Stephen J.
中科院分区:
文献类型:
--
作者:
Jin, Zhe;Zhao, Zhenfu;Cheng, Yulan;Dong, Ming;Zhang, Xiaojing;Wang, Liang;Fan, Xinmin;Feng, Xianling;Mori, Yuriko;Meltzer, Stephen J.
Endoglin (ENG) is a 180-kDa 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. We examined ENG promoter hypermethylation using real-time quantitative methylation-specific PCR in 260 human esophageal tissues. ENG hypermethylation showed highly discriminative receiver-operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) from normal esophagus (N) (p<0.01). Interestingly, ENG normalized methylation values were significantly higher in ESCC than in N (p<0.01) or EAC (p<0.01). ENG hypermethylation frequency was 46.2% in ESCC and 11.9% in N, but increased early and sequentially during EAC-associated neoplastic progression, to 13.3% in Barrett’s metaplasia (BE), 25% in dysplastic BE (D), and 26.9% in frank EAC. ENG hypermethylation was significantly higher in N from ESCC patients (mean = 0.0186) than in N from EAC patients (mean = 0.0117; p < 0.05). Treatment of KYSE220 ESCC cells with the demethylating agent, 5-aza-2′-deoxycytidine, reversed ENG methylation and reactivated ENG mRNA expression. We conclude that promoter hypermethylation of ENG is 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.
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影响因子:
24.5
作者:
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通讯作者:
Matsubara, N.
影响因子:
2.8
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Wikström, P;Lissbrandt, IF;Bergh, A
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8
作者:
Jin, Z.;Mori, Y.;Meltzer, S. J.
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Meltzer, S. J.
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8
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通讯作者:
Meltzer, SJ
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29.4
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通讯作者:
Meltzer, Stephen J.