Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, PN, Italy.
Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy.
Gastric Cancer. 2021 May;24(3):666-679. doi: 10.1007/s10120-020-01148-3. Epub 2021 Feb 23.
Autoimmune atrophic gastritis (AAG) is a chronic disease that can progress to gastric cancer (GC). To better understand AAG pathology, this proteomics study investigated gastric proteins whose expression levels are altered in this disease and also in GC.
Using two-dimensional difference gel electrophoresis (2D-DIGE), we compared protein maps of gastric corpus biopsies from AAG patients and controls. Differentially abundant spots (|fold change|≥ 1.5, P < 0.01) were selected and identified by LC-MS/MS. The spots were further assessed in gastric antrum biopsies from AAG patients (without and with Helicobacter pylori infection) and from GC patients and unaffected first-degree relatives of GC patients.
2D-DIGE identified 67 differentially abundant spots, with 28 more and 39 less abundant in AAG-corpus than controls. LC-MS/MS identified these as 53 distinct proteins. The most significant (adjusted P < 0.01) biological process associated with the less abundant proteins was "tricarboxylic acid cycle". Of the 67 spots, 57 were similarly differentially abundant in AAG-antrum biopsies irrespective of H. pylori infection status. The differential abundance was also observed in GC biopsies for 14 of 28 more abundant and 35 of 39 less abundant spots, and in normal gastric biopsies of relatives of GC patients for 6 and 25 spots, respectively. Immunoblotting confirmed the different expression levels of two more abundant proteins (PDIA3, GSTP gene products) and four less abundant proteins (ATP5F1A, PGA3, SDHB, PGC).
This study identified a proteomics signature of AAG. Many differential proteins were shared by GC and may be involved in the progression of AAG to GC.
自身免疫性萎缩性胃炎（AAG）是一种可进展为胃癌（GC）的慢性疾病。为了更好地了解 AAG 病理学，本蛋白质组学研究调查了在这种疾病和 GC 中表达水平改变的胃蛋白。
使用二维差异凝胶电泳（2D-DIGE），我们比较了 AAG 患者和对照组胃体活检的蛋白质图谱。选择差异丰富的斑点（|倍数变化|≥1.5，P<0.01），并通过 LC-MS/MS 进行鉴定。这些斑点在 AAG 患者（无和有幽门螺杆菌感染）和 GC 患者以及 GC 患者的无影响一级亲属的胃窦活检中进一步评估。
2D-DIGE 鉴定出 67 个差异丰富的斑点，其中 AAG 胃体比对照组多 28 个，少 39 个。LC-MS/MS 将这些鉴定为 53 种不同的蛋白质。与较少丰富的蛋白质相关的最显著（调整 P<0.01）生物学过程是“三羧酸循环”。在 67 个斑点中，57 个在 AAG 胃窦活检中无论 H. pylori 感染状态如何都具有相似的差异丰富度。在 GC 活检中，28 个更丰富的斑点中有 14 个和 39 个更少丰富的斑点中有 35 个观察到差异丰富度，在 GC 患者的正常胃活检中，分别有 6 个和 25 个斑点观察到差异丰富度。免疫印迹证实了两种更丰富的蛋白质（PDIA3、GSTP 基因产物）和四种较少丰富的蛋白质（ATP5F1A、PGA3、SDHB、PGC）的不同表达水平。
本研究确定了 AAG 的蛋白质组学特征。许多差异蛋白与 GC 共享，可能参与 AAG 向 GC 的进展。
