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


Journal

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
ISSN: 1436-3305
Titre abrégé: Gastric Cancer
Pays: Japan
ID NLM: 100886238

Informations de publication

Date de publication:
May 2021
Historique:
received: 31 07 2020
accepted: 09 12 2020
pubmed: 24 2 2021
medline: 21 12 2021
entrez: 23 2 2021
Statut: ppublish

Résumé

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.

Sections du résumé

BACKGROUND 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 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 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 CONCLUSIONS
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.

Identifiants

pubmed: 33620602
doi: 10.1007/s10120-020-01148-3
pii: 10.1007/s10120-020-01148-3
pmc: PMC8064991
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

666-679

Subventions

Organisme : Italian Minister of Health
ID : reference number RF-2016-02361525

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Auteurs

Ombretta Repetto (O)

Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, PN, Italy. orepetto@cro.it.

Valli De Re (V)

Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, PN, Italy. vdere@cro.it.

Paolo Giuffrida (P)

Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy.

Marco Vincenzo Lenti (MV)

Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy.

Raffaella Magris (R)

Gastroenterology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, PN, Italy.

Marino Venerito (M)

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany.

Agostino Steffan (A)

Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, PN, Italy.

Antonio Di Sabatino (A)

Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy.

Renato Cannizzaro (R)

Gastroenterology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, PN, Italy.

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