Reduction of prostaglandin transporter predicts poor prognosis associated with angiogenesis in gastric adenocarcinoma

Abstract

PGT expression is an independent predictor of poor survival and is associated with tumor angiogenesis in gastric adenocarcinoma.

Whole Genome Messenger RNA Profiling Identifies a Novel Signature to Predict Gastric Cancer Survival

“…In addition, a DCLK1 -based mRNA signature has also been established previously to predict GC survival (26). However, negative SLCO2A1 (also known as PGT) protein expression in GC tumor specimens (n = 96), as examined by immunohistochemistry, was associated with poor survival (27), in contrast to our findings on the inverse association between SLCO2A1 mRNA expression and GC survival. As that study was conducted based on a limited sample size, and also lacked a validation stage, the robustness of that finding may be of concern.…”

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

“…Furthermore, the immunohistochemical staining showed a diffuse SLCO2A1 expression in normal gland epithelial cells of the stomach, similar to other expression patterns reported previously in normal intestinal cells and suggesting a strict regulation of PGE 2 concentration to maintain cellular homeostasis [ 53 ]. The authors presume that this homeostasis is impaired in gastric tumors due to the negative regulation of SLCO2A1 and, consequently, the negative regulation of PGE 2 degradation, resulting in the enhancement of PGE 2 signaling and gastric tumorigenesis [ 53 ]. Contrary to those reports, a study by Nakanishi et al [ 54 ] suggests an association between higher SLCO2A1 expression in colorectal cancer and poor prognosis.…”

“…In the same study, by Bujok et al [ 52 ], a higher expression of the protein was found in GC tissue compared to normal tissue, but with no statistical significance. Takeda et al [ 53 ] were the first to identify SLCO2A1 expression as an independent predictor of poor prognosis in patients with GC. In this study, reduction of the transporter expression correlated with increased tumor angiogenesis and its suppression by specific small interfering RNA (siRNA) promoted the production of vascular endothelial growth factor (VEGF), a mediator of angiogenesis, induced by PGE 2 [ 53 ].…”

“…Takeda et al [ 53 ] were the first to identify SLCO2A1 expression as an independent predictor of poor prognosis in patients with GC. In this study, reduction of the transporter expression correlated with increased tumor angiogenesis and its suppression by specific small interfering RNA (siRNA) promoted the production of vascular endothelial growth factor (VEGF), a mediator of angiogenesis, induced by PGE 2 [ 53 ]. Furthermore, the immunohistochemical staining showed a diffuse SLCO2A1 expression in normal gland epithelial cells of the stomach, similar to other expression patterns reported previously in normal intestinal cells and suggesting a strict regulation of PGE 2 concentration to maintain cellular homeostasis [ 53 ].…”

“…In this study, reduction of the transporter expression correlated with increased tumor angiogenesis and its suppression by specific small interfering RNA (siRNA) promoted the production of vascular endothelial growth factor (VEGF), a mediator of angiogenesis, induced by PGE 2 [ 53 ]. Furthermore, the immunohistochemical staining showed a diffuse SLCO2A1 expression in normal gland epithelial cells of the stomach, similar to other expression patterns reported previously in normal intestinal cells and suggesting a strict regulation of PGE 2 concentration to maintain cellular homeostasis [ 53 ]. The authors presume that this homeostasis is impaired in gastric tumors due to the negative regulation of SLCO2A1 and, consequently, the negative regulation of PGE 2 degradation, resulting in the enhancement of PGE 2 signaling and gastric tumorigenesis [ 53 ].…”