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

Chantal A Ten Kate; Annelies de Klein; Bianca M de Graaf; Michail Doukas; Antti Koivusalo; Mikko P Pakarinen; Robert van der Helm; Tom Brands; Hanneke IJsselstijn; Yolande van Bever; René M H Wijnen; Manon C W Spaander; Erwin Brosens

doi:10.3390/cancers14030513

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

Chantal A Ten Kate, Annelies de Klein, Bianca M de Graaf, Michail Doukas, Antti Koivusalo, Mikko P Pakarinen, Robert van der Helm, Tom Brands, Hanneke IJsselstijn, Yolande van Bever, René M H Wijnen, Manon C W Spaander, Erwin Brosens^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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 (n = 19, EA/BE); EA patients without BE (n = 44, EA-only) and BE patients without EA (n = 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.

Original language	English
Article number	513
Journal	Cancers
Volume	14
Issue number	3
DOIs	https://doi.org/10.3390/cancers14030513
Publication status	Published - 20 Jan 2022

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Intrinsic Cellular Susceptibility to Barrett’s Esophagus in Adults Born with Esophageal AtresiaFinal published version, 1.56 MBLicence: CC BY

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Ten Kate, C. A., de Klein, A., de Graaf, B. M., Doukas, M., Koivusalo, A., Pakarinen, M. P., van der Helm, R., Brands, T., IJsselstijn, H., van Bever, Y., Wijnen, R. M. H., Spaander, M. C. W., & Brosens, E. (2022). Intrinsic Cellular Susceptibility to Barrett's Esophagus in Adults Born with Esophageal Atresia. Cancers, 14(3), Article 513. https://doi.org/10.3390/cancers14030513

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abstract = "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 (n = 19, EA/BE); EA patients without BE (n = 44, EA-only) and BE patients without EA (n = 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.",

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AU - Koivusalo, Antti

AU - Pakarinen, Mikko P

AU - van der Helm, Robert

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AU - IJsselstijn, Hanneke

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AU - Wijnen, René M H

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AU - Brosens, Erwin

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N2 - 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 (n = 19, EA/BE); EA patients without BE (n = 44, EA-only) and BE patients without EA (n = 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.

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

Abstract

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