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Open Access Green as soon as Postprint is submitted to ZB.
Goblet cell ratio in combination with differentiation and stem cell markers in barrett esophagus allow distinction of patients with and without esophageal adenocarcinoma.
Cancer Prev. Res. 10, 55-66 (2017)
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The increasing incidence of esophageal adenocarcinoma (EAC) is mirrored by the increasing prevalence of Barrett esophagus, a precursor lesion resulting in a large number of individuals "at risk" for this lethal malignancy. Among patients with Barrett esophagus, only about 0.3% annually will develop EAC. Because large numbers of patients are followed in endoscopic surveillance, there is a need for risk prediction among a growing population of patients with Barrett esophagus. We identified four potential biomarkers from an inflammation (IL1b)-dependent mouse model of Barrett esophagus and tested them in 189 patients with Barrett esophagus with and without high-grade dysplasia (HGD)/ early cancer (T1). The primary goal was to distinguish patients with Barrett esophagus with no evidence of dysplasia from those with dysplasia. Increasing stem cell marker LGR5 and niche cell marker DCLK1 and decreasing differentiation marker (secretory mucus cells, TFF2+ cells) correlated with elevated tumor score in the mouse. Having outlined the origin of those markers in the Barrett esophagus mouse model, we showed the applicability for human Barrett esophagus. We compared 94 patients with nondysplastic Barrett esophagus tissue with 95 patients with Barrett esophagus and HGD or early cancer. Low levels of TFF2 (AUC 87.2%) provided the best discrimination between nondysplastic Barrett esophagus and Barrett esophagus with cancer, followed by high levels of DCLK1 (AUC 83.4%), low goblet cell ratio (AUC 79.4%), and high LGR5 (AUC 71.4%). The goblet cell ratio, rather than the presence of goblet cells per se, was found to be an important discriminator. These findings may be useful in developing future risk prediction models for patients with Barrett esophagus and ultimately to improve EAC surveillance.
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Times Cited
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3.985
0.979
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Gene-expression Profile; Intestinal Metaplasia; Columnar Epithelium; Mouse Model; Cancer; Identification; Origin; Lgr5; Tff2; Progression
Language
Publication Year
2017
Prepublished in Year
2016
HGF-reported in Year
2016
ISSN (print) / ISBN
1940-6207
e-ISSN
1940-6215
Journal
Cancer Prevention Research
Quellenangaben
Volume: 10,
Issue: 1,
Pages: 55-66
Publisher
American Association for Cancer Research (AACR)
Publishing Place
Philadelphia
Reviewing status
Peer reviewed
Institute(s)
Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology (EPI)
Institute of Epidemiology (EPI)
POF-Topic(s)
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-504100-001
G-504000-005
G-504000-005
WOS ID
WOS:000393694500005
Scopus ID
85009193412
PubMed ID
27807078
Erfassungsdatum
2016-12-31