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Prostaglandin E(2) Pathway Is Dysregulated in Gastric Adenocarcinoma in a Caucasian Population

Gastric cancer (GC) represents the third leading cause of cancer-related deaths worldwide. The levels of prostaglandin E(2), a key player in the hallmarks of cancer, are mainly regulated by prostaglandin-endoperoxide synthase 2 (PTGS2) and ATP-binding cassette subfamily C member 4 (ABCC4), involved...

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Autores principales: Lopes, Catarina, Pereira, Carina, Farinha, Mónica, Medeiros, Rui, Dinis-Ribeiro, Mário
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589882/
https://www.ncbi.nlm.nih.gov/pubmed/33081378
http://dx.doi.org/10.3390/ijms21207680
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author Lopes, Catarina
Pereira, Carina
Farinha, Mónica
Medeiros, Rui
Dinis-Ribeiro, Mário
author_facet Lopes, Catarina
Pereira, Carina
Farinha, Mónica
Medeiros, Rui
Dinis-Ribeiro, Mário
author_sort Lopes, Catarina
collection PubMed
description Gastric cancer (GC) represents the third leading cause of cancer-related deaths worldwide. The levels of prostaglandin E(2), a key player in the hallmarks of cancer, are mainly regulated by prostaglandin-endoperoxide synthase 2 (PTGS2) and ATP-binding cassette subfamily C member 4 (ABCC4), involved in its synthesis and exportation, respectively, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and solute carrier organic anion transporter family member 2A1 (SLCO2A1), responsible for its inactivation. Even though there are distinct molecular signatures across ethnic populations, most published studies focus on Asian populations. Our main aim was to explore the genetic expression of the aforementioned molecules in a Caucasian population. 94 “Normal” and 89 tumoral formalin-fixed paraffin-embedded (FFPE) samples from GC patients were used to assess the mRNA expression of PTGS2, ABCC4, hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD), SLCO2A1 by Real-Time PCR. We found an upregulation for the PTGS2 gene mean factor of 2.51 and a downregulation for the HPGD and SLCO2A1 genes (mean factor of 0.10 and 0.37, respectively) in tumorous mucosa in a gender-independent manner. In females, we observed an ABCC4 downregulation and a PTGS2 mRNA upregulation compared to males in tumoral mucosa (mean factor of 0.61 and 1.64, respectively). We reported dysregulation of the inflammation triggered PGE(2) pathway in a Caucasian population with an intermediate risk for GC, which might highlight the applicability of aspirin in the treatment of GC patients.
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spelling pubmed-75898822020-10-29 Prostaglandin E(2) Pathway Is Dysregulated in Gastric Adenocarcinoma in a Caucasian Population Lopes, Catarina Pereira, Carina Farinha, Mónica Medeiros, Rui Dinis-Ribeiro, Mário Int J Mol Sci Article Gastric cancer (GC) represents the third leading cause of cancer-related deaths worldwide. The levels of prostaglandin E(2), a key player in the hallmarks of cancer, are mainly regulated by prostaglandin-endoperoxide synthase 2 (PTGS2) and ATP-binding cassette subfamily C member 4 (ABCC4), involved in its synthesis and exportation, respectively, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and solute carrier organic anion transporter family member 2A1 (SLCO2A1), responsible for its inactivation. Even though there are distinct molecular signatures across ethnic populations, most published studies focus on Asian populations. Our main aim was to explore the genetic expression of the aforementioned molecules in a Caucasian population. 94 “Normal” and 89 tumoral formalin-fixed paraffin-embedded (FFPE) samples from GC patients were used to assess the mRNA expression of PTGS2, ABCC4, hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD), SLCO2A1 by Real-Time PCR. We found an upregulation for the PTGS2 gene mean factor of 2.51 and a downregulation for the HPGD and SLCO2A1 genes (mean factor of 0.10 and 0.37, respectively) in tumorous mucosa in a gender-independent manner. In females, we observed an ABCC4 downregulation and a PTGS2 mRNA upregulation compared to males in tumoral mucosa (mean factor of 0.61 and 1.64, respectively). We reported dysregulation of the inflammation triggered PGE(2) pathway in a Caucasian population with an intermediate risk for GC, which might highlight the applicability of aspirin in the treatment of GC patients. MDPI 2020-10-16 /pmc/articles/PMC7589882/ /pubmed/33081378 http://dx.doi.org/10.3390/ijms21207680 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lopes, Catarina
Pereira, Carina
Farinha, Mónica
Medeiros, Rui
Dinis-Ribeiro, Mário
Prostaglandin E(2) Pathway Is Dysregulated in Gastric Adenocarcinoma in a Caucasian Population
title Prostaglandin E(2) Pathway Is Dysregulated in Gastric Adenocarcinoma in a Caucasian Population
title_full Prostaglandin E(2) Pathway Is Dysregulated in Gastric Adenocarcinoma in a Caucasian Population
title_fullStr Prostaglandin E(2) Pathway Is Dysregulated in Gastric Adenocarcinoma in a Caucasian Population
title_full_unstemmed Prostaglandin E(2) Pathway Is Dysregulated in Gastric Adenocarcinoma in a Caucasian Population
title_short Prostaglandin E(2) Pathway Is Dysregulated in Gastric Adenocarcinoma in a Caucasian Population
title_sort prostaglandin e(2) pathway is dysregulated in gastric adenocarcinoma in a caucasian population
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589882/
https://www.ncbi.nlm.nih.gov/pubmed/33081378
http://dx.doi.org/10.3390/ijms21207680
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