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

International Journal of Molecular Sciences

卷:21

Mário Dinis-Ribeiro¹  Rui Medeiros²  Catarina Lopes²  Carina Pereira²  Mónica Farinha³ 

[1] CINTESIS–Center for Health Technology and Services Research, University of Porto, 4200-450, Porto, Portugal;

[2] Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal;

[3] Pathology Department, Portuguese Institute of Oncology, 4200-072 Porto, Portugal;

关键词: gastric cancer;    mRNA expression;    prostaglandin E;    prostaglandin-endoperoxide synthase 2;    hydroxyprostaglandin dehydrogenase 15-(NAD);    solute carrier organic anion transporter family member 2A1;   

DOI  :  10.3390/ijms21207680

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown