Intrinsic Cellular Susceptibility to Barrett's Esophagus in Adults Born with Esophageal Atresia

• Published in: Cancers Vol. 14; no. 3; p. 513
• Main Authors: Ten Kate, Chantal A, de Klein, Annelies, de Graaf, Bianca M, Doukas, Michail, Koivusalo, Antti, Pakarinen, Mikko P, van der Helm, Robert, Brands, Tom, IJsselstijn, Hanneke, van Bever, Yolande, Wijnen, René M H, Spaander, Manon C W, Brosens, Erwin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.01.2022; MDPI
• Subjects: acid sensitivity; Biobanks; Biopsy; Cellular stress response; Diagnostic tests; Esophageal cancer; Esophageal carcinoma; esophagitis; Esophagus; Fibroblasts; Foregut; Gastroesophageal reflux; Gene expression; genetic predisposition; Genomes; Homeostasis; Immune response; Inflammation; inflammatory response; Patients; Population; Retinoic acid; Signal transduction; Single-nucleotide polymorphism; Surveillance; Transcriptomes; United States > US; Netherlands; genetic predisposition; inflammatory response; acid sensitivity; esophageal carcinoma; esophagitis
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14030513

The prevalence of Barrett's esophagus (BE) in adults born with esophageal atresia (EA) is four times higher than in the general population and presents at a younger age (34 vs. 60 years). This is (partly) a consequence of chronic gastroesophageal reflux. Given the overlap between genes and pathways involved in foregut and BE development, we hypothesized that EA patients have an intrinsic predisposition to develop BE. Transcriptomes of Esophageal biopsies of EA patients with BE ( = 19, EA/BE); EA patients without BE ( = 44, EA-only) and BE patients without EA ( = 10, BE-only) were compared by RNA expression profiling. Subsequently, we simulated a reflux episode by exposing fibroblasts of 3 EA patients and 3 controls to acidic conditions. Transcriptome responses were compared to the differential expressed transcripts in the biopsies. Predisposing single nucleotide polymorphisms, associated with BE, were slightly increased in EA/BE versus BE-only patients. RNA expression profiling and pathway enrichment analysis revealed differences in retinoic acid metabolism and downstream signaling pathways and inflammatory, stress response and oncological processes. There was a similar effect on retinoic acid signaling and immune response in EA patients upon acid exposure. These results indicate that epithelial tissue homeostasis in EA patients is more prone to acidic disturbances.