title: Reduction of prostaglandin transporter predicts poor prognosis associated with angiogenesis in gastric adenocarcinoma.
abstract: OBJECTIVE
  Prostaglandin (PG) E2 promotes gastrointestinal carcinogenesis and tumor progression. The total amount of biologically active PGE2 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 PGE2 .
  
  
  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 PGE2 in the culture media.
  
  
  CONCLUSIONS
  PGT expression is an independent predictor of poor survival and is associated with tumor angiogenesis in gastric adenocarcinoma.
authors.affiliation: Departments of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka City, Osaka, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Takeda
authors.affiliation: Departments of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka City, Osaka, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tanigawa
authors.affiliation: Departments of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka City, Osaka, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Departments of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka City, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tatsuwaki
authors.affiliation: Departments of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka City, Osaka, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nadatani
authors.affiliation: Departments of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka City, Osaka, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Otani
authors.affiliation: Departments of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka City, Osaka, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Nagami
authors.affiliation: Departments of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka City, Osaka, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Tanaka
authors.affiliation: Departments of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka City, Osaka, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kamata
authors.affiliation: Departments of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka City, Osaka, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Yamagami
authors.affiliation: Departments of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka City, Osaka, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Shiba
authors.affiliation: Departments of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka City, Osaka, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tominaga
authors.affiliation: Departments of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka City, Osaka, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka City, Osaka, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Muguruma
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka City, Osaka, Japan.
authors.forename: Masaichi
authors.initials: M
authors.lastname: Ohira
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka City, Osaka, Japan.
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa
authors.affiliation: Departments of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka City, Osaka, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Arakawa
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply* / Q000401:mortality; D015232:Dinoprostone / Q000378:metabolism / Q000502:physiology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D055806:Microvessels / Q000473:pathology; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011379:Prognosis; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000401:mortality; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D027361:Organic Anion Transporters; C503526:SLCO2A1 protein, human; D042461:Vascular Endothelial Growth Factor A; D015232:Dinoprostone
keywords: 15-hydroxyprostaglandin dehydrogenase; gastric cancer; prostaglandin transporter; univariate and multivariate analysis; vascular endothelial growth factor