Prostaglandin E2 Pathway Is Dysregulated in Gastric Adenocarcinoma in a Caucasian Population.

Abstract

Gastric cancer (GC) represents the third leading cause of cancer-related deaths worldwide. The levels of prostaglandin E2, 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 PGE2 pathway in a Caucasian population with an intermediate risk for GC, which might highlight the applicability of aspirin in the treatment of GC patients.

• Authors: Catarina Lopes, Carina Pereira, Mónica Farinha, Rui Medeiros, Mário Dinis-Ribeiro
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 20 (Oct 16 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 33081378 (Publication Type: Journal Article)

Chemical References

• ABCC4 protein, human
• Multidrug Resistance-Associated Proteins
• Organic Anion Transporters
• SLCO2A1 protein, human
• Hydroxyprostaglandin Dehydrogenases
• 15-hydroxyprostaglandin dehydrogenase
• Cyclooxygenase 2
• PTGS2 protein, human
• Dinoprostone

Topics

• Adenocarcinoma (genetics, metabolism)
• Aged
• Cyclooxygenase 2 (genetics, metabolism)
• Dinoprostone (genetics, metabolism)
• Female
• Gastric Mucosa (metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Hydroxyprostaglandin Dehydrogenases (genetics, metabolism)
• Male
• Multidrug Resistance-Associated Proteins (genetics, metabolism)
• Organic Anion Transporters (genetics, metabolism)
• Stomach Neoplasms (genetics, metabolism)