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BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

Temporal evolution in caveolin 1 methylation levels during human esophageal carcinogenesis

Authors: Zhe Jin, Liang Wang, Ziyi Cao, Yulan Cheng, Yan Gao, Xianling Feng, Si Chen, Huimin Yu, Wenjing Wu, Zhenfu Zhao, Ming Dong, Xiaojing Zhang, Jie Liu, Xinmin Fan, Yuriko Mori, Stephen J Meltzer

Published in: BMC Cancer | Issue 1/2014

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Abstract

Background

Esophageal cancer ranks eighth among frequent cancers worldwide. Our aim was to investigate whether and at which neoplastic stage promoter hypermethylation of CAV1 is involved in human esophageal carcinogenesis.

Methods

Using real-time quantitative methylation-specific PCR (qMSP), we examined CAV1 promoter hypermethylation in 260 human esophageal tissue specimens. Real-time RT-PCR and qMSP were also performed on OE33 esophageal cancer cells before and after treatment with the demethylating agent, 5-aza-2’-deoxycytidine (5-Aza-dC).

Results

CAV1 hypermethylation showed highly discriminative ROC curve profiles, clearly distinguishing esophageal adenocarcinomas (EAC) and esophageal squamous cell carcinomas (ESCC) from normal esophagus (NE) (EAC vs. NE, AUROC = 0.839 and p < 0.0001; ESCC vs. NE, AUROC = 0.920 and p < 0.0001). Both CAV1 methylation frequency and normalized methylation value (NMV) were significantly higher in Barrett’s metaplasia (BE), low-grade and high-grade dysplasia occurring in BE (D), EAC, and ESCC than in NE (all p < 0.01, respectively). Meanwhile, among 41 cases with matched NE and EAC or ESCC, CAV1 NMVs in EAC and ESCC (mean = 0.273) were significantly higher than in corresponding NE (mean = 0.146; p < 0.01, Student’s paired t-test). Treatment of OE33 EAC cells with 5-Aza-dC reduced CAV1 methylation and increased CAV1 mRNA expression.

Conclusions

CAV1 promoter hypermethylation is a frequent event in human esophageal carcinomas and is associated with early neoplastic progression in Barrett’s esophagus.
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Metadata
Title
Temporal evolution in caveolin 1 methylation levels during human esophageal carcinogenesis
Authors
Zhe Jin
Liang Wang
Ziyi Cao
Yulan Cheng
Yan Gao
Xianling Feng
Si Chen
Huimin Yu
Wenjing Wu
Zhenfu Zhao
Ming Dong
Xiaojing Zhang
Jie Liu
Xinmin Fan
Yuriko Mori
Stephen J Meltzer
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-345

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