643 In Esophageal Epithelium, the Transcription Factor FOXA2 is a Hedgehog Target Gene That May Mediate Columnar Metaplasia, as Occurs in Barrett's Esophagus

Background and Aims Because of the extremely low neoplastic progression rate in Barrett's esophagus, it is difficult to diagnose patients with concomitant adenocarcinoma early in their disease course. If biomarkers existed in normal squamous esophageal epithelium to identify patients with concomitant esophageal adenocarcinoma, potential applications would be far-reaching. The aim of the current study was to identify global gene expression patterns in normal esophageal epithelium capable of revealing simultaneous esophageal adenocarcinoma, even located remotely in the esophagus. Methods Tissues comprised normal esophageal epithelia from 9 patients with esophageal adenocarcinoma, 8 patients lacking esophageal adenocarcinoma or Barrett's, and 6 patients with Barrett's esophagus alone. cDNA microarrays were performed, and pattern recognition in each of these subgroups was achieved using shrunken nearest centroid predictors. Results Our method accurately discriminated normal esophageal epithelia of 8/8 patients without esophageal adenocarcinoma or Barrett's esophagus and of 6/6 patients with Barrett's esophagus alone from normal esophageal epithelia of 9/9 patients with Barrett's esophagus and concomitant esophageal adenocarcinoma. Moreover, we identified genes differentially expressed between the above subgroups. Thus, based on their corresponding normal esophageal epithelia alone, our method accurately diagnosed patients who had concomitant esophageal adenocarcinoma. Conclusions These global gene expression patterns, along with individual genes culled from them, represent potential biomarkers for the early diagnosis of esophageal adenocarcinoma from normal esophageal epithelia. Genes discovered in normal esophagus that are differentially expressed in patients with vs. without esophageal adenocarcinoma merit further pursuit in molecular genetic, functional, and therapeutic interventional studies.

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A renewed insight into Barrett's esophagus: comparative histopathological analysis of esophageal columnar metaplasia

Diseases of the Esophagus ◽

10.1111/j.1442-2050.2011.01270.x ◽

2011 ◽

Vol 25 (5) ◽

pp. 395-402 ◽

Cited By ~ 5

Author(s):

I. B. Nemeth ◽

A. Rosztoczy ◽

F. Izbeki ◽

R. Roka ◽

K. Gecse ◽

...

Keyword(s):

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Histopathological Analysis ◽

Columnar Metaplasia ◽

Insight Into

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Discrepancies and pitfalls in diagnosis and therapy of esophageal columnar metaplasia/Barrett's esophagus: A personal view

Journal of Digestive Diseases ◽

10.1111/1751-2980.12071 ◽

2013 ◽

Vol 14 (8) ◽

pp. 405-408

Author(s):

Guido NJ Tytgat

Keyword(s):

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Personal View ◽

Diagnosis And Therapy ◽

Columnar Metaplasia

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Notch Signaling Pathway Is Inhibited in the Development of Barrett’s Esophagus: An In Vivo and In Vitro Study

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2018/4149317 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11

Author(s):

Yun-Cang Wang ◽

Zhi-Qiang Wang ◽

Yong Yuan ◽

Tao Ren ◽

Peng-Zhi Ni ◽

...

Keyword(s):

Hydrochloric Acid ◽

Notch Signaling ◽

Signaling Pathway ◽

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Deoxycholic Acid ◽

Notch Signaling Pathway ◽

Normal Esophagus ◽

Columnar Metaplasia

Objective. To explore the role of Notch signaling in the development of Barrett’s esophagus. Methods. Patients with esophagectomy and gastric interposition were recruited as a human model of gastroesophageal reflux disease. The expressions of Notch signaling genes in normal esophagus from surgical specimen and columnar metaplasia in the esophageal remnant after esophagectomy were evaluated by real time quantitative Polymerase Chain Reaction (RT-qPCR) and immunohistochemistry (IHC). For in vitro experiments, Het-1A cells were treated with hydrochloric acid, deoxycholic acid, mixture of hydrochloric acid and deoxycholic acid, or Notch1-siRNA, and expressions of Notch1, Hes1, MUC2, and K13 were evaluated via RT-qPCR and western blot. Results. Samples were obtained from 36 patients with columnar metaplasia in the esophageal remnant. Both IHC and RT-qPCR indicated that Notch1 and Hes1 expressions were significantly higher in normal esophagus than that in metaplasia. Hydrochloric acid and deoxycholic acid suppressed Notch1, Hes1, and K13 expressions, in concert with increasing MUC2 expressions. Notch inhibition by Notch1-siRNA contributed to the downregulation of Notch1, Hes1, and K13 expressions, whereas MUC2 expression was enhanced. Conclusions. Both hydrochloric acid and deoxycholic acid could suppress Notch signaling pathway in esophageal epithelial cells, and inhibited Notch signaling has important functions in the development of Barrett’s esophagus.

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