title: Examining the connectivity between different cellular processes in the Barrett tissue microenvironment.
abstract: In Barrett associated tumorigenesis, oxidative phosphorylation and glycolysis are reprogrammed early in the disease sequence and act mutually to promote disease progression. However, the link between energy metabolism and its connection with other central cellular processes within the Barrett microenvironment is unknown. The aim of this study was to examine the relationship between metabolism (ATP5B/GAPDH), hypoxia (HIF1α), inflammation (IL1β/SERPINA3), p53 and obesity status using in-vivo and ex-vivo models of Barrett oesophagus. At the protein level, ATP5B (r = 0.71, P < 0.0001) and p53 (r = 0.455, P = 0.015) were found to be strongly associated with hypoxia. In addition, levels of ATP5B (r = 0.53, P = 0.0031) and GAPDH (r = -0.39, P = 0.0357) were positively associated with p53 expression. Moreover, we demonstrate that ATP5B (r = 0.8, P < 0.0001) and GAPDH (r = 0.43, P = 0.022) were positively associated with IL1β expression. Interestingly, obesity was negatively associated with oxidative phosphorylation (r = -0.6016, P = 0.0177) but positively associated with glycolysis (r = 0.743, P = 0.0015). Comparable correlations were exhibited in the ex-vivo explant tissue between metabolism, p53, hypoxia, inflammation and angiogenesis (P < 0.05). We have shown that metabolism is closely linked with many cellular processes in the Barrett tissue microenvironment.
authors.affiliation: Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin, Ireland.
authors.forename: J J
authors.initials: JJ
authors.lastname: Phelan
authors.affiliation: Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin, Ireland.
authors.forename: R
authors.initials: R
authors.lastname: Feighery
authors.affiliation: Department of Histopathology, St. James's Hospital, Dublin, Ireland.
authors.forename: O S
authors.initials: OS
authors.lastname: Eldin
authors.affiliation: Centre for Health Decision Science (CHeDS), School of Computer Science and Statistics, Trinity College Dublin, Dublin, Ireland.
authors.forename: S Ó
authors.initials: SÓ
authors.lastname: Meachair
authors.affiliation: Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin, Ireland.
authors.forename: A
authors.initials: A
authors.lastname: Cannon
authors.affiliation: Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin, Ireland.
authors.forename: R
authors.initials: R
authors.lastname: Byrne
authors.affiliation: Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin, Ireland.
authors.forename: F
authors.initials: F
authors.lastname: MacCarthy
authors.affiliation: Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin, Ireland.
authors.forename: D
authors.initials: D
authors.lastname: O'Toole
authors.affiliation: Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin, Ireland.
authors.forename: J V
authors.initials: JV
authors.lastname: Reynolds
authors.affiliation: Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin, Ireland. Electronic address: osullij4@tcd.ie.
authors.forename: J
authors.initials: J
authors.lastname: O'Sullivan
mesh_terms: D000368:Aged; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D002450:Cell Communication; D015687:Cell Hypoxia; D002460:Cell Line; D060833:Cellular Microenvironment; D004947:Esophagus / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D009389:Neovascularization, Pathologic; D009765:Obesity / Q000378:metabolism; D010085:Oxidative Phosphorylation; D011446:Prospective Studies; D015843:Serpins / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C506526:ATP5F1B protein, human; D015415:Biomarkers; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C508585:IL1B protein, human; D018836:Inflammation Mediators; D053583:Interleukin-1beta; C516148:SERPINA3 protein, human; D015843:Serpins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D025261:Mitochondrial Proton-Translocating ATPases
keywords: Barrett oesophagus; Glycolysis; Hypoxia; Inflammation; Obesity; Oxidative phosphorylation