Original Article: MicroRNA Dysregulation in the Gastric Carcinogenesis Cascade: Can We Anticipate Its Role in Individualized Care?


Journal

Pathobiology : journal of immunopathology, molecular and cellular biology
ISSN: 1423-0291
Titre abrégé: Pathobiology
Pays: Switzerland
ID NLM: 9007504

Informations de publication

Date de publication:
2021
Historique:
received: 27 01 2021
accepted: 01 03 2021
pubmed: 19 7 2021
medline: 8 1 2022
entrez: 18 7 2021
Statut: ppublish

Résumé

Gastric carcinogenesis progresses from normal mucosa, atrophic/metaplastic gastritis, and dysplasia to adenocarcinoma. MicroRNAs (miRNAs) regulate DNA expression and have been implicated; however, their role is not fully established. The aim of this study was to characterize plasma and tissue expression of several miRNAs in gastric carcinogenesis stages. Single-center cross-sectional study in 64 patients: 19 controls (normal mucosa); 15 with extensive atrophic/metaplastic gastritis; and 30 with early gastric neoplasia (EGN). Seven miRNAs (miR-21, miR-146a, miR-181b, miR-370, miR-375, miR 181b, and miR-490) were quantified by real time-qPCR in peripheral blood and endoscopic biopsy samples. We found a significant upregulation of miR-181b, miR-490, and miR-21 in the EGN mucosa (overexpression 2-14-times higher than controls). We observed a significant underexpression of miR-146a and miR-370 in atrophic/metaplastic gastritis (86 and 66% decrease, p = 0.008 and p = 0.001) and in EGN (89 and 62% reduction, p = 0.034 and p = 0.032) compared with controls. There were no differences between lesions and nonneoplastic mucosa and no dysregulation of plasma miRNAs. We found significant dysregulation of 5 miRNAs in gastric carcinogenesis, suggesting a tumor suppressor role for miR-146a and miR-370 and oncogenic potential for miR-21, miR-181, and miR-490. These changes happen diffusely in the gastric mucosa, suggesting a high-risk field defect, which may influence these patients' surveillance.

Sections du résumé

BACKGROUND BACKGROUND
Gastric carcinogenesis progresses from normal mucosa, atrophic/metaplastic gastritis, and dysplasia to adenocarcinoma. MicroRNAs (miRNAs) regulate DNA expression and have been implicated; however, their role is not fully established.
AIMS OBJECTIVE
The aim of this study was to characterize plasma and tissue expression of several miRNAs in gastric carcinogenesis stages.
METHODS METHODS
Single-center cross-sectional study in 64 patients: 19 controls (normal mucosa); 15 with extensive atrophic/metaplastic gastritis; and 30 with early gastric neoplasia (EGN). Seven miRNAs (miR-21, miR-146a, miR-181b, miR-370, miR-375, miR 181b, and miR-490) were quantified by real time-qPCR in peripheral blood and endoscopic biopsy samples.
RESULTS RESULTS
We found a significant upregulation of miR-181b, miR-490, and miR-21 in the EGN mucosa (overexpression 2-14-times higher than controls). We observed a significant underexpression of miR-146a and miR-370 in atrophic/metaplastic gastritis (86 and 66% decrease, p = 0.008 and p = 0.001) and in EGN (89 and 62% reduction, p = 0.034 and p = 0.032) compared with controls. There were no differences between lesions and nonneoplastic mucosa and no dysregulation of plasma miRNAs.
CONCLUSION CONCLUSIONS
We found significant dysregulation of 5 miRNAs in gastric carcinogenesis, suggesting a tumor suppressor role for miR-146a and miR-370 and oncogenic potential for miR-21, miR-181, and miR-490. These changes happen diffusely in the gastric mucosa, suggesting a high-risk field defect, which may influence these patients' surveillance.

Identifiants

pubmed: 34274936
pii: 000515548
doi: 10.1159/000515548
doi:

Substances chimiques

MicroRNAs 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

338-350

Informations de copyright

© 2021 S. Karger AG, Basel.

Auteurs

Inês Pita (I)

Gastroenterology Department, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.

Diogo Libânio (D)

Gastroenterology Department, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.
MEDCIDS - Department of Community Medicine, Health Information and Decision of the Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal.

Francisca Dias (F)

Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.
Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Porto, Portugal.

Ana Luísa Teixeira (AL)

Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.

Inês Nogueira (I)

Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.
Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Porto, Portugal.
Research Department of the Portuguese League Against Cancer Regional Nucleus of the North (LPCC-NRN), Porto, Portugal.

Rui Medeiros (R)

Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.
Research Department of the Portuguese League Against Cancer Regional Nucleus of the North (LPCC-NRN), Porto, Portugal.
Faculty of Medicine, University of Porto (FMUP), Porto, Portugal.
Biomedical Research Center (CEBIMED), Faculty of Health Sciences of the Fernando Pessoa University (UFP), Porto, Portugal.

Mário Dinis-Ribeiro (M)

Gastroenterology Department, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.
MEDCIDS - Department of Community Medicine, Health Information and Decision of the Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal.

Pedro Pimentel-Nunes (P)

Gastroenterology Department, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.
MEDCIDS - Department of Community Medicine, Health Information and Decision of the Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal.

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Classifications MeSH