TY - JOUR
T1 - The molecular signature of normal squamous esophageal epithelium identifies the presence of a field effect and can discriminate between patients with Barrett's esophagus and patients with Barrett's-associated adenocarcinoma
AU - Brabender, Jan
AU - Marjoram, Paul
AU - Lord, Reginald V.N.
AU - Metzger, Ralf
AU - Salonga, Dennis
AU - Vallböhmer, Daniel
AU - Schäfer, Hartmut
AU - Danenberg, Kathleen D.
AU - Danenberg, Peter V.
AU - Selaru, Florin M.
AU - Baldus, Stefan E.
AU - Hölscher, Arnulf H.
AU - Meltzer, Stephen J.
AU - Schneider, Paul M.
PY - 2005/9
Y1 - 2005/9
N2 - Background and Aim: Genetic alterations in the normal tissues surrounding various cancers have been described, but a comprehensive analysis of this carcinogenic field effect in Barrett's-associated adenocarcinoma of the esophagus disease has not been reported. The aim of this study was to analyze the gene expression profile of a panel of highly selected genes in the normal squamous esophagus epihelium of patients with Barrett's esophagus, patients with Barrett's-associated adenocarcinoma, and a healthy control group to define the existence of a carcinogenic field effect, and to investigate the clinical importance of such a field effect in the management of Barrett's disease. Methods: Forty-nine histologic normal squamous esophageal epithelia collected from 19 patients with Barrett's esophagus, 20 patients with Barrett's-associated esophageal adenocarcinoma, and a healthy control group of 10 patients were studied. A quantitative real-time reverse transcription-PCR method (TaqMan) was used to measure the expression of a panel of genes with known associations with gastrointestinal carcinogenesis. Results: A widespread carcinogenic field effect was detected for more than 50% of the genes analyzed including Bax, BFT, CDX2, COX2, DAPK, DNMT1, GSTP1, RARα, RARγ, RXRα, RXRβ, SPARC, TSPAN, and VEGF. Based on the expression signature of the normal appearing squamous esophagus, a linear discriminant analysis was able to distinguish between the three groups of patients with an error rate of 0%. Conclusion: This study provides the first comprehensive investigation of a carcinogenic field effect in Barrett's esophagus disease. Based on the gene expression signature of the normal esophagus, patients could be correctly characterized according to their pathologic classification by applying a linear discriminant analysis. Our results provide evidence that a molecular classification might have clinical importance for the diagnosis and treatment of patients with Barrett's esophagus disease.
AB - Background and Aim: Genetic alterations in the normal tissues surrounding various cancers have been described, but a comprehensive analysis of this carcinogenic field effect in Barrett's-associated adenocarcinoma of the esophagus disease has not been reported. The aim of this study was to analyze the gene expression profile of a panel of highly selected genes in the normal squamous esophagus epihelium of patients with Barrett's esophagus, patients with Barrett's-associated adenocarcinoma, and a healthy control group to define the existence of a carcinogenic field effect, and to investigate the clinical importance of such a field effect in the management of Barrett's disease. Methods: Forty-nine histologic normal squamous esophageal epithelia collected from 19 patients with Barrett's esophagus, 20 patients with Barrett's-associated esophageal adenocarcinoma, and a healthy control group of 10 patients were studied. A quantitative real-time reverse transcription-PCR method (TaqMan) was used to measure the expression of a panel of genes with known associations with gastrointestinal carcinogenesis. Results: A widespread carcinogenic field effect was detected for more than 50% of the genes analyzed including Bax, BFT, CDX2, COX2, DAPK, DNMT1, GSTP1, RARα, RARγ, RXRα, RXRβ, SPARC, TSPAN, and VEGF. Based on the expression signature of the normal appearing squamous esophagus, a linear discriminant analysis was able to distinguish between the three groups of patients with an error rate of 0%. Conclusion: This study provides the first comprehensive investigation of a carcinogenic field effect in Barrett's esophagus disease. Based on the gene expression signature of the normal esophagus, patients could be correctly characterized according to their pathologic classification by applying a linear discriminant analysis. Our results provide evidence that a molecular classification might have clinical importance for the diagnosis and treatment of patients with Barrett's esophagus disease.
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U2 - 10.1158/1055-9965.EPI-05-0014
DO - 10.1158/1055-9965.EPI-05-0014
M3 - Article
C2 - 16172218
AN - SCOPUS:27744608217
SN - 1055-9965
VL - 14
SP - 2113
EP - 2117
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 9
ER -