Genome-wide methylation analysis shows similar patterns in Barrett's esophagus and esophageal adenocarcinoma

Enping Xu, Jian Gu, Ernest T. Hawk, Kenneth Ke Ning Wang, Maode Lai, Maosheng Huang, Jaffer Ajani, Xifeng Wu

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Barrett's esophagus (BE) is a precursor of esophageal adenocarcinoma (EAC). To identify novel tumor suppressors involved in esophageal carcinogenesis and potential biomarkers for the malignant progression of BE, we performed a genome-wide methylation profiling of BE and EAC tissues. Using Illumina's Infinium HumanMethylation27 BeadChip microarray, we examined the methylation status of 27 578 CpG sites in 94 normal esophageal (NE), 77 BE and 117 EAC tissue samples. The overall methylation of CpG sites within the CpG islands was higher, but outside of the CpG islands was lower in BE and EAC tissues than in NE tissues. Hierarchical clustering analysis showed an excellent separation of NE tissues from BE and EAC tissues; however, the clustering of BE and EAC tissues was less clear, suggesting that methylation occurs early during the progression of EAC. We confirmed many previously reported hypermethylated genes and identified a large number of novel hypermethylated genes in BE and EAC tissues, particularly genes encoding ADAM (A Disintegrin And Metalloproteinase) peptidase proteins, cadherins and protocadherins, and potassium voltage-gated channels. Pathway analysis showed that a number of channel and transporter activities were enriched for hypermethylated genes. We used pyrosequencing to validate selected candidate genes and found high correlations between the array and pyrosequencing data (rho > 0.8 for each validated gene). The differentially methylated genes and pathways may provide biological insights into the development and progression of BE and become potential biomarkers for the prediction and early detection of EAC.

Original languageEnglish (US)
Pages (from-to)2750-2756
Number of pages7
JournalCarcinogenesis
Volume34
Issue number12
DOIs
StatePublished - Dec 2013

Fingerprint

Barrett Esophagus
Methylation
Adenocarcinoma
Genome
Genes
CpG Islands
Cluster Analysis
Biomarkers
Disintegrins
Voltage-Gated Potassium Channels
Metalloproteases
Cadherins
Carcinogenesis
Peptide Hydrolases

ASJC Scopus subject areas

  • Cancer Research

Cite this

Genome-wide methylation analysis shows similar patterns in Barrett's esophagus and esophageal adenocarcinoma. / Xu, Enping; Gu, Jian; Hawk, Ernest T.; Wang, Kenneth Ke Ning; Lai, Maode; Huang, Maosheng; Ajani, Jaffer; Wu, Xifeng.

In: Carcinogenesis, Vol. 34, No. 12, 12.2013, p. 2750-2756.

Research output: Contribution to journalArticle

Xu, Enping ; Gu, Jian ; Hawk, Ernest T. ; Wang, Kenneth Ke Ning ; Lai, Maode ; Huang, Maosheng ; Ajani, Jaffer ; Wu, Xifeng. / Genome-wide methylation analysis shows similar patterns in Barrett's esophagus and esophageal adenocarcinoma. In: Carcinogenesis. 2013 ; Vol. 34, No. 12. pp. 2750-2756.
@article{915bf449cf37447f963c970c189270d4,
title = "Genome-wide methylation analysis shows similar patterns in Barrett's esophagus and esophageal adenocarcinoma",
abstract = "Barrett's esophagus (BE) is a precursor of esophageal adenocarcinoma (EAC). To identify novel tumor suppressors involved in esophageal carcinogenesis and potential biomarkers for the malignant progression of BE, we performed a genome-wide methylation profiling of BE and EAC tissues. Using Illumina's Infinium HumanMethylation27 BeadChip microarray, we examined the methylation status of 27 578 CpG sites in 94 normal esophageal (NE), 77 BE and 117 EAC tissue samples. The overall methylation of CpG sites within the CpG islands was higher, but outside of the CpG islands was lower in BE and EAC tissues than in NE tissues. Hierarchical clustering analysis showed an excellent separation of NE tissues from BE and EAC tissues; however, the clustering of BE and EAC tissues was less clear, suggesting that methylation occurs early during the progression of EAC. We confirmed many previously reported hypermethylated genes and identified a large number of novel hypermethylated genes in BE and EAC tissues, particularly genes encoding ADAM (A Disintegrin And Metalloproteinase) peptidase proteins, cadherins and protocadherins, and potassium voltage-gated channels. Pathway analysis showed that a number of channel and transporter activities were enriched for hypermethylated genes. We used pyrosequencing to validate selected candidate genes and found high correlations between the array and pyrosequencing data (rho > 0.8 for each validated gene). The differentially methylated genes and pathways may provide biological insights into the development and progression of BE and become potential biomarkers for the prediction and early detection of EAC.",
author = "Enping Xu and Jian Gu and Hawk, {Ernest T.} and Wang, {Kenneth Ke Ning} and Maode Lai and Maosheng Huang and Jaffer Ajani and Xifeng Wu",
year = "2013",
month = "12",
doi = "10.1093/carcin/bgt286",
language = "English (US)",
volume = "34",
pages = "2750--2756",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "12",

}

TY - JOUR

T1 - Genome-wide methylation analysis shows similar patterns in Barrett's esophagus and esophageal adenocarcinoma

AU - Xu, Enping

AU - Gu, Jian

AU - Hawk, Ernest T.

AU - Wang, Kenneth Ke Ning

AU - Lai, Maode

AU - Huang, Maosheng

AU - Ajani, Jaffer

AU - Wu, Xifeng

PY - 2013/12

Y1 - 2013/12

N2 - Barrett's esophagus (BE) is a precursor of esophageal adenocarcinoma (EAC). To identify novel tumor suppressors involved in esophageal carcinogenesis and potential biomarkers for the malignant progression of BE, we performed a genome-wide methylation profiling of BE and EAC tissues. Using Illumina's Infinium HumanMethylation27 BeadChip microarray, we examined the methylation status of 27 578 CpG sites in 94 normal esophageal (NE), 77 BE and 117 EAC tissue samples. The overall methylation of CpG sites within the CpG islands was higher, but outside of the CpG islands was lower in BE and EAC tissues than in NE tissues. Hierarchical clustering analysis showed an excellent separation of NE tissues from BE and EAC tissues; however, the clustering of BE and EAC tissues was less clear, suggesting that methylation occurs early during the progression of EAC. We confirmed many previously reported hypermethylated genes and identified a large number of novel hypermethylated genes in BE and EAC tissues, particularly genes encoding ADAM (A Disintegrin And Metalloproteinase) peptidase proteins, cadherins and protocadherins, and potassium voltage-gated channels. Pathway analysis showed that a number of channel and transporter activities were enriched for hypermethylated genes. We used pyrosequencing to validate selected candidate genes and found high correlations between the array and pyrosequencing data (rho > 0.8 for each validated gene). The differentially methylated genes and pathways may provide biological insights into the development and progression of BE and become potential biomarkers for the prediction and early detection of EAC.

AB - Barrett's esophagus (BE) is a precursor of esophageal adenocarcinoma (EAC). To identify novel tumor suppressors involved in esophageal carcinogenesis and potential biomarkers for the malignant progression of BE, we performed a genome-wide methylation profiling of BE and EAC tissues. Using Illumina's Infinium HumanMethylation27 BeadChip microarray, we examined the methylation status of 27 578 CpG sites in 94 normal esophageal (NE), 77 BE and 117 EAC tissue samples. The overall methylation of CpG sites within the CpG islands was higher, but outside of the CpG islands was lower in BE and EAC tissues than in NE tissues. Hierarchical clustering analysis showed an excellent separation of NE tissues from BE and EAC tissues; however, the clustering of BE and EAC tissues was less clear, suggesting that methylation occurs early during the progression of EAC. We confirmed many previously reported hypermethylated genes and identified a large number of novel hypermethylated genes in BE and EAC tissues, particularly genes encoding ADAM (A Disintegrin And Metalloproteinase) peptidase proteins, cadherins and protocadherins, and potassium voltage-gated channels. Pathway analysis showed that a number of channel and transporter activities were enriched for hypermethylated genes. We used pyrosequencing to validate selected candidate genes and found high correlations between the array and pyrosequencing data (rho > 0.8 for each validated gene). The differentially methylated genes and pathways may provide biological insights into the development and progression of BE and become potential biomarkers for the prediction and early detection of EAC.

UR - http://www.scopus.com/inward/record.url?scp=84888993325&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84888993325&partnerID=8YFLogxK

U2 - 10.1093/carcin/bgt286

DO - 10.1093/carcin/bgt286

M3 - Article

VL - 34

SP - 2750

EP - 2756

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 12

ER -