scholarly journals Proteomics signature of autoimmune atrophic gastritis: towards a link with gastric cancer

2021 ◽  
Author(s):  
Ombretta Repetto ◽  
Valli De Re ◽  
Paolo Giuffrida ◽  
Marco Vincenzo Lenti ◽  
Raffaella Magris ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Atrophic Gastritis ◽  
Tricarboxylic Acid Cycle ◽  
Differential Abundance ◽  
Expression Levels ◽  
2D Dige ◽  
Gastric Corpus ◽  
Gastric Biopsies ◽  
H Pylori ◽  
Autoimmune Atrophic Gastritis

Abstract Background 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. Methods 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. Results 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). Conclusion 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.

scholarly journals Polymorphism in Toll-Like Receptors and Helicobacter Pylori Motility in Autoimmune Atrophic Gastritis and Gastric Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 648 ◽  
Author(s):  
Valli De Re ◽  
Ombretta Repetto ◽  
Mariangela De Zorzi ◽  
Mariateresa Casarotto ◽  
Massimo Tedeschi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Atrophic Gastritis ◽  
Toll Like Receptors ◽  
Innate And Adaptive Immunity ◽  
Healthy Donors ◽  
Increased Risk ◽  
Host Cell Interactions ◽  
H Pylori ◽  
Autoimmune Atrophic Gastritis

Autoimmune atrophic gastritis (AAG) is associated with an increased risk of certain types of gastric cancer (GC). Helicobacter pylori (H. pylori) infection may have a role in the induction and/or maintenance of AAG and GC. Toll-like receptors (TLR) are essential for H. pylori recognition and subsequent innate and adaptive immunity responses. This study therefore aimed to characterize TLR polymorphisms, and features of bacterial flagellin A in samples from patients with AAG (n = 67), GC (n = 114) and healthy donors (HD; n = 97). TLR5 rs5744174 C/C genotype was associated with GC, lower IgG anti H. pylori response and a higher H. pylori flagellin A abundance and motility. In a subset of patients with AAG, H. pylori strains showed a reduction of the flagellin A abundance and a moderate motility compared with strains from GC patients, a prerequisite for active colonization of the deeper layers of the mucosa, host immune response and inflammation. TLR9 rs5743836 T allele showed an association with serum gastrin G17. In conclusion, our study suggests that alterations of flaA protein, moderate motility in H. pylori and two polymorphisms in TLR5 and TLR9 may favor the onset of AAG and GC, at least in a subset of patients. These findings corroborate the function of pathogen–host cell interactions and responses, likely influencing the pathogenetic process.

scholarly journals Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use

2017 ◽  
Author(s):  
Bryony N. Parsons ◽  
Umer Zeeshan Ijaz ◽  
Rosalinda D’Amore ◽  
Michael D. Burkitt ◽  
Richard Eccles ◽  
...  
Keyword(s):  
Proton Pump Inhibitor ◽  
Microbial Diversity ◽  
Atrophic Gastritis ◽  
Proton Pump ◽  
List Type ◽  
Gastric Corpus ◽  
H Pylori ◽  
Autoimmune Atrophic Gastritis ◽  
Gastric Malignancy ◽  
Gastric Microbiota

ABSTRACTObjectiveSeveral conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI) use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk.Design95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis) were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq).ResultsSamples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase.ConclusionAutoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects.SIGNIFICANCE OF THIS STUDY1.What is already known about this subject?Some conditions which result in reduced gastric acid secretion and hypochlorhydria are associated with an increased risk of gastric tumourigenesis.This risk is different in patients with H. pylori-induced atrophic gastritis, autoimmune atrophic gastritis and chronic proton pump inhibitor use.Hypochlorhydria and H. pylori infection cause alterations in the composition of the gastric microbiota.2.What are the new findings?We used 16S rRNA sequencing to characterise the microbiota in gastric corpus biopsies from a well characterised cohort of patients.The gastric microbiota was different in patients who were hypochlorhydric as a result of H. pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use.Biochemical pathways associated with gastric carcinogenesis such as the fumarate reductase pathway were predicted to be altered in patients with atrophic gastritis.3.How might it impact on clinical practice in the foreseeable future?Understanding how the microbiota that colonise the hypochlorhydric stomach influence gastric carcinogenesis may ultimately permit stratification of patients’ subsequent tumour risk.Interventions that alter the composition of the gastric microbiome in hypochlorhydric patients with atrophic gastritis should be tested to investigate whether they alter the subsequent risk of developing gastric malignancy.

scholarly journals Chronic Gastritis in Dermatitis Herpetiformis: A Controlled Study

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Anna Alakoski ◽  
Teea T. Salmi ◽  
Kaisa Hervonen ◽  
Hannu Kautiainen ◽  
Maarit Salo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Atrophic Gastritis ◽  
Intestinal Metaplasia ◽  
Chronic Gastritis ◽  
Dermatitis Herpetiformis ◽  
Villous Atrophy ◽  
Chronic Atrophic Gastritis ◽  
Controlled Study ◽  
Gastric Corpus ◽  
H Pylori

Background and Objective. Previous small studies suggest that chronic atrophic gastritis is common in dermatitis herpetiformis (DH). We here examined the frequency and topography of chronic gastritis in 93 untreated DH subjects and in 186 controls with dyspepsia.Methods. Specimens were drawn from the gastric corpus and antrum and examined for atrophy, intestinal metaplasia, andHelicobacter pylori. Duodenal biopsies were taken.Results. Atrophic corpus gastritis was more frequent in DH than in controls (16.0% and 2.7%, resp.,P<0.001); atrophy in the antrum was rare in both groups (3.2% and 1.1%,P=0.34). Intestinal metaplasia was present in 13 (14.0%) DH and 12 (6.5%) control patients (P=0.038) andH. pyloriin 17 (18.3%) and 17 (9.3%) (P=0.028), respectively. Small-bowel villous atrophy was seen in 76% of the DH patients, equally in patients with and without chronic gastritis. One DH patient with atrophic gastritis developed gastric cancer.Conclusion. In DH, chronic atrophic gastritis was common in the corpus, but not in the antrum.H. pyloriwill partly explain this, but corpus atrophy is suggestive of an autoimmune etiology. Atrophic gastritis may increase the risk of gastric cancer. We advocate performing upper endoscopy with sufficient histologic samples in DH.

TLR1 and PRKAA1 Gene Polymorphisms in the Development of Atrophic Gastritis and Gastric Cancer

2018 ◽  
Vol 27 (4) ◽  
pp. 363-369 ◽  
Author(s):  
Gintare Dargiene ◽  
Greta Streleckiene ◽  
Jurgita Skieceviciene ◽  
Marcis Leja ◽  
Alexander Link ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Atrophic Gastritis ◽  
Genetic Polymorphisms ◽  
Association Studies ◽  
Control Group ◽  
Similar Distribution ◽  
Genome Wide Association Studies ◽  
Increased Risk ◽  
Infection Susceptibility ◽  
H Pylori

Background & Aims: Previous genome-wide association studies showed that genetic polymorphisms in toll-like receptor 1 (TLR1) and protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) genes were associated with gastric cancer (GC) or increased Helicobacter pylori (H. pylori) infection susceptibility. The aim of this study was to evaluate the association between TLR1 and PRKAA1 genes polymorphisms and H.pylori infection, atrophic gastritis (AG) or GC in the European population.Methods: Single-nucleotide polymorphisms (SNPs) were analysed in 511 controls, 340 AG patients and 327 GC patients. TLR1 C>T (rs4833095) and PRKAA1 C>T (rs13361707) were genotyped by the real-time polymerase chain reaction. H. pylori status was determined by testing for anti-H. pylori IgG antibodies in the serum.Results: The study included 697 (59.2%) H. pylori positive and 481 (40.8%) H. pylori negative cases. We observed similar distribution of TLR1 and PRKAA1 alleles and genotypes in H. pylori positive and negative cases. TLR1 and PRKAA1 SNPs were not linked with the risk of AG. TC genotype of TLR1 gene was more prevalent in GC patients compared to the control group (29.7% and 22.3% respectively, p=0.002). Carriers of TC genotype had a higher risk of GC (aOR=1.89, 95% CI: 1.26–2.83, p=0.002). A similar association was observed in a dominant inheritance model for TLR1 gene SNP, where comparison of CC+TC vs. TT genotypes showed an increased risk of GC (aOR=1.86, 95% CI: 1.26–2.75, p=0.002). No association between genetic polymorphism in PRKAA1 gene and GC was observed.Conclusions: TLR1 rs4833095 SNP was associated with an increased risk of GC in a European population, while PRKAA1 rs13361707 genetic variant was not linked with GC. Both genetic polymorphisms were not associated with H. pylori infection susceptibility or the risk of AG.

scholarly journals Two Cases of White Globe Appearance in Autoimmune Atrophic Gastritis

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Masaya Iwamuro ◽  
Takehiro Tanaka ◽  
Hiromitsu Kanzaki ◽  
Seiji Kawano ◽  
Yoshiro Kawahara ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Atrophic Gastritis ◽  
Parietal Cells ◽  
Microscopic Features ◽  
Autoimmune Atrophic Gastritis ◽  
Necrotic Debris

In this report, we described two patients with white globe appearance in autoimmune atrophic gastritis. Endoscopy revealed multiple white substances in the stomach in both cases. Biopsied specimens from the lesions contained dilated glands and showed a decrease in parietal cells. Intraglandular necrotic debris and carcinoma were absent. These results confirmed that white globe appearance can be observed in autoimmune atrophic gastritis. Moreover, microscopic features for white globe appearance observed in these cases were different from those reported previously in gastric cancer lesions and were similar to those observed for noncancerous stomach.

Multifocal Early Gastric Cancer in a Patient with Autoimmune Atrophic Gastritis and Iron Deficiency Anaemia

2009 ◽  
Vol 30 (03) ◽  
pp. 139-143
Author(s):  
A. Neesse ◽  
P. Michl ◽  
P. Barth ◽  
M. Vieth ◽  
P. Langer ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Iron Deficiency ◽  
Early Gastric Cancer ◽  
Atrophic Gastritis ◽  
Iron Deficiency Anaemia ◽  
Deficiency Anaemia ◽  
Autoimmune Atrophic Gastritis

scholarly journals Eradication of Helicobacter pylori and Gastric Cancer: A Controversial Relationship

2021 ◽  
Vol 12 ◽  
Author(s):  
Mariagrazia Piscione ◽  
Mariangela Mazzone ◽  
Maria Carmela Di Marcantonio ◽  
Raffaella Muraro ◽  
Gabriella Mincione
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Atrophic Gastritis ◽  
Precancerous Lesions ◽  
Eradication Therapy ◽  
Developed Countries ◽  
Gastric Carcinogenesis ◽  
Gastric Disease ◽  
Type I ◽  
H Pylori

Worldwide, gastric cancer (GC) represents the fifth cancer for incidence, and the third as cause of death in developed countries. Indeed, it resulted in more than 780,000 deaths in 2018. Helicobacter pylori appears to be responsible for the majority of these cancers. On the basis of recent studies, and either alone or combined with additional etiological factors, H. pylori is considered a “type I carcinogen.” Over recent decades, new insights have been obtained into the strategies that have been adopted by H. pylori to survive the acidic conditions of the gastric environment, and to result in persistent infection, and dysregulation of host functions. The multistep processes involved in the development of GC are initiated by transition of the mucosa into chronic non-atrophic gastritis, which is primarily triggered by infection with H. pylori. This gastritis then progresses into atrophic gastritis and intestinal metaplasia, and then to dysplasia, and following Correa’s cascade, to adenocarcinoma. The use of antibiotics for eradication of H. pylori can reduce the incidence of precancerous lesions only in the early stages of gastric carcinogenesis. Here, we first survey the etiology and risk factors of GC, and then we analyze the mechanisms underlying tumorigenesis induced by H. pylori, focusing attention on virulence factor CagA, inflammation, oxidative stress, and ErbB2 receptor tyrosine kinase. Moreover, we investigate the relationships between H. pylori eradication therapy and other diseases, considering not only cardia (upper stomach) cancers and Barrett’s esophagus, but also asthma and allergies, through discussion of the “hygiene hypothesis. ” This hypothesis suggests that improved hygiene and antibiotic use in early life reduces microbial exposure, such that the immune response does not become primed, and individuals are not protected against atopic disorders, asthma, and autoimmune diseases. Finally, we overview recent advances to uncover the complex interplay between H. pylori and the gut microbiota during gastric carcinogenesis, as characterized by reduced bacterial diversity and increased microbial dysbiosis. Indeed, it is of particular importance to identify the bacterial taxa of the stomach that might predict the outcome of gastric disease through the stages of Correa’s cascade, to improve prevention and therapy of gastric carcinoma.

AF.22 PROTEOMICS SIGNATURE OF AUTOIMMUNE ATROPHIC GASTRITIS: TOWARDS A LINK WITH GASTRIC CANCER

2021 ◽  
Vol 53 ◽  
pp. S147
Author(s):  
O. Repetto ◽  
V. De Re ◽  
P. Giuffrida ◽  
M.V. Lenti ◽  
R. Magris ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Atrophic Gastritis ◽  
Autoimmune Atrophic Gastritis
Sign in / Sign up

Export Citation Format

Share Document