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Temporal evolution in caveolin 1 methylation levels during human esophageal carcinogenesis
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 ex...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4035847/ https://www.ncbi.nlm.nih.gov/pubmed/24885118 http://dx.doi.org/10.1186/1471-2407-14-345 |
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author | Jin, Zhe Wang, Liang Cao, Ziyi Cheng, Yulan Gao, Yan Feng, Xianling Chen, Si Yu, Huimin Wu, Wenjing Zhao, Zhenfu Dong, Ming Zhang, Xiaojing Liu, Jie Fan, Xinmin Mori, Yuriko Meltzer, Stephen J |
author_facet | Jin, Zhe Wang, Liang Cao, Ziyi Cheng, Yulan Gao, Yan Feng, Xianling Chen, Si Yu, Huimin Wu, Wenjing Zhao, Zhenfu Dong, Ming Zhang, Xiaojing Liu, Jie Fan, Xinmin Mori, Yuriko Meltzer, Stephen J |
author_sort | Jin, Zhe |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4035847 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-40358472014-05-29 Temporal evolution in caveolin 1 methylation levels during human esophageal carcinogenesis Jin, Zhe Wang, Liang Cao, Ziyi Cheng, Yulan Gao, Yan Feng, Xianling Chen, Si Yu, Huimin Wu, Wenjing Zhao, Zhenfu Dong, Ming Zhang, Xiaojing Liu, Jie Fan, Xinmin Mori, Yuriko Meltzer, Stephen J BMC Cancer Research Article 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. BioMed Central 2014-05-20 /pmc/articles/PMC4035847/ /pubmed/24885118 http://dx.doi.org/10.1186/1471-2407-14-345 Text en Copyright © 2014 Jin et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Jin, Zhe Wang, Liang Cao, Ziyi Cheng, Yulan Gao, Yan Feng, Xianling Chen, Si Yu, Huimin Wu, Wenjing Zhao, Zhenfu Dong, Ming Zhang, Xiaojing Liu, Jie Fan, Xinmin Mori, Yuriko Meltzer, Stephen J Temporal evolution in caveolin 1 methylation levels during human esophageal carcinogenesis |
title | Temporal evolution in caveolin 1 methylation levels during human esophageal carcinogenesis |
title_full | Temporal evolution in caveolin 1 methylation levels during human esophageal carcinogenesis |
title_fullStr | Temporal evolution in caveolin 1 methylation levels during human esophageal carcinogenesis |
title_full_unstemmed | Temporal evolution in caveolin 1 methylation levels during human esophageal carcinogenesis |
title_short | Temporal evolution in caveolin 1 methylation levels during human esophageal carcinogenesis |
title_sort | temporal evolution in caveolin 1 methylation levels during human esophageal carcinogenesis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4035847/ https://www.ncbi.nlm.nih.gov/pubmed/24885118 http://dx.doi.org/10.1186/1471-2407-14-345 |
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