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

Background and Aim:Prostaglandin (PG) E-2 promotes gastrointestinal carcinogenesis and tumor progression. The total amount of biologically active PGE(2) in tissues is determined by a balance of PG biosynthesis and degradation pathways, which involve the PG transporter (PGT). We investigated PGT in gastric adenocarcinoma by determining its expression pattern and examining associations of PGT with prognosis and tumor angiogenesis. Methods:PGT expression was determined by immunohistochemistry in advanced gastric adenocarcinoma specimens obtained from 96 patients who underwent surgical resection. Correlations between PGT expression level and clinicopathological factors were statistically analyzed. Angiogenesis in the tumor tissue was evaluated by counting the number of microvessels. The role of PGT in mRNA and protein expression of vascular endothelial growth factor (VEGF) was examined in gastric cancer cells stimulated by PGE(2). Results:Based on multivariate and Kaplan-Meier analyses, negativity for PGT expression was an independent poor prognostic factor. There were more microvessels in PGT-negative tumors than in PGT-positive tumors. Transfection of AGS and MKN7 gastric cancer cells with PGT-specific siRNA led to increased VEGF mRNA and protein expression accompanied by increased PGE(2) in the culture media. Conclusions:PGT expression is an independent predictor of poor survival and is associated with tumor angiogenesis in gastric adenocarcinoma.