Proteome-Wide Analysis Using SOMAscan Identifies and Validates Epidermal Growth Factor as a Disease Marker of Collagenous Gastritis

Abstract

Background and Aims: Collagenous gastritis (CG) is a rare disorder characterized by increased subepithelial collagen deposition and inflammatory infiltrates. The mechanisms involved in CG pathogenesis are poorly understood, and no CG-associated biomarkers have been identified. This proteomics study identified serum biomarkers and pathogenic pathways to provide new knowledge about the pathobiology of CG, a disease reported in less than 100 patients. Methods: Nine serum samples from pediatric patients diagnosed with CG were evaluated using novel aptamer-based proteomic technology and systems biology to generate new knowledge about the complex interactions between the differentially expressed proteins and candidate upstream regulators, using the Ingenuity Pathway Analysis in patients with non-CG and patients with normal gastric biopsies or nongastritis (NG). Results: SOMAscan analysis identified 63 proteins significantly dysregulated in CG as compared to non-CG or NG patients that converged around enhanced inflammatory response and immune cell migration but reduced vascular functions. Principal component analysis using 15 of those proteins accurately separated the CG cases from the 2 comparator control groups. Using immunoassays, serum epidermal growth factor concentrations in CG patients, a protein involved in collagen production, were confirmed to be significantly lower than those in gastritis/NG patients. Conclusion: This is the first comprehensive analysis of the proteome in CG patients that reveals metabolic pathways relating inflammation and fibrosis as well as a new potential role of epidermal growth factor as a disease biomarker.

Keywords

• Collagenous Gastritis
• Proteomics
• Biomarker
• Epidermal Growth Factor