Curci Debora, Dillon Simon T, Gu Xuesong, Winter Harland, Libermann Towia A
Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Advanced Diagnostic and Translational Medicine Laboratory, Trieste, Italy.
Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Gastro Hep Adv. 2022 Apr 28;1(5):689-702. doi: 10.1016/j.gastha.2022.04.016. eCollection 2022.
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.
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).
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.
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.
胶原性胃炎（CG）是一种罕见疾病，其特征为上皮下胶原沉积增加和炎症浸润。CG发病机制尚不清楚，且未发现与CG相关的生物标志物。这项蛋白质组学研究旨在鉴定血清生物标志物和致病途径，以提供有关CG病理生物学的新知识，CG患者报告不足100例。
使用基于新型适配体的蛋白质组学技术和系统生物学对9例诊断为CG的儿科患者的血清样本进行评估，通过对非CG患者以及胃活检正常或无胃炎（NG）患者进行 Ingenuity 通路分析，了解差异表达蛋白与候选上游调节因子之间复杂的相互作用。
SOMAscan分析确定，与非CG或NG患者相比，CG中有63种蛋白质显著失调，这些蛋白质集中在增强的炎症反应和免疫细胞迁移，但血管功能降低方面。使用其中15种蛋白质进行主成分分析，可准确地将CG病例与2个对照比较组区分开来。通过免疫测定法证实，CG患者血清表皮生长因子浓度（一种参与胶原蛋白产生的蛋白质）显著低于胃炎/NG患者。
这是首次对CG患者蛋白质组进行的全面分析，揭示了炎症和纤维化相关的代谢途径以及表皮生长因子作为疾病生物标志物的新潜在作用。
