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- 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; Meltzer, Stephen J.
- 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.
- Subjects
ESOPHAGEAL cancer; CAVEOLINS; METHYLATION; POLYMERASE chain reaction; SQUAMOUS cell carcinoma; DEOXYCYTIDINE
- Publication
BMC Cancer, 2014, Vol 14, p1
- ISSN
1471-2407
- Publication type
Article
- DOI
10.1186/1471-2407-14-345