Abstract
Helicobacter pylori is an important risk factor of gastric cancer (GC). Although many H. pylori virulence factors have been reported, the pathogenic mechanism by which H. pylori infection causes GC remains unclear. The aims of this study were to identify GC-related antigens from H. pylori and characterize their roles in the development of GC. As GC and duodenal ulcer (DU) are considered clinically divergent, we compared two-dimensional immunoblots of an acid-glycine extract of H. pylori probed with serum samples from 15 patients with GC and 15 with DU to find GC-related antigens, which were subsequently identified by mass spectrometry. Many protein spots were recognized by more than one serum, and 24 of these were better recognized by GC sera. The proteins showing higher frequency of recognition in GC group are threonine synthase, rod shape-determining protein, S-adenosylmethionine synthetase, peptide chain release factor 1, DNA-directed RNA polymerase alpha subunit, co-chaperonin GroES (monomeric and dimeric forms), response regulator OmpR, and membrane fusion protein. Of these proteins, GroES was identified as a dominant GC-related antigen with a much higher seropositivity of GC samples (64.2%, n = 95) compared with 30.9% for gastritis (n = 94) and 35.5% for DU (n = 124). GroES seropositivity was more commonly associated with antral GC than with non-antral GC (odds ratio = 2.7; 95% confidence interval, 1.1-6.7). In peripheral blood mononuclear cells, GroES stimulated production of interleukin (IL)-8, IL-6, granulocyte macrophage colony-stimulating factor, IL-1beta, tumor necrosis factor-alpha, cyclooxygenase-2, and prostaglandin E(2). Moreover when incubated with gastric epithelial cells, GroES induced expression of IL-8, cell proliferation, and up-regulation of c-jun, c-fos, and cyclin D1 but caused down-regulation of p27(Kip1). We conclude that GroES of H. pylori is a novel GC-associated virulence factor and may contribute to gastric carcinogenesis via induction of inflammation and promotion of cell proliferation.
Highlights
Helicobacter pylori is an important risk factor of gastric cancer (GC)
To characterize candidate H. pylori antigens associated with GC, we used a proteomic approach for the global detection of H. pylori antigens recognized by serum IgG from GC patients
A serological study showed that 64.2% of GC sera reacted with H. pylori GroES compared with 30.9% of gastritis samples and 35.5% of duodenal ulcer (DU) samples and that there was no significant difference in GroES seropositivity between the early and advanced stages of GC
Summary
Helicobacter pylori is an important risk factor of gastric cancer (GC). many H. pylori virulence factors have been reported, the pathogenic mechanism by which H. pylori infection causes GC remains unclear. The proteins showing higher frequency of recognition in GC group are threonine synthase, rod shape-determining protein, S-adenosylmethionine synthetase, peptide chain release factor 1, DNAdirected RNA polymerase ␣ subunit, co-chaperonin GroES (monomeric and dimeric forms), response regulator OmpR, and membrane fusion protein Of these proteins, GroES was identified as a dominant GC-related antigen with a much higher seropositivity of GC samples (64.2%, n ؍95) compared with 30.9% for gastritis (n ؍94) and 35.5% for DU (n ؍124). Two studies reported the identification of candidate antigens of H. pylori associated with DU and GC by comparing the profiles of 2D immunoblots probed with DU and GC sera [11, 12] In both studies, differentially recognized antigens were determined by spot intensity, which might be biased by variations in the immune response in different diseases and in different. The serological responses toward these proteins imply that these antigens are recognized, processed, or presented by human antigen-presenting cells for initiating immune response
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