title: GIPR expression in gastric and duodenal neuroendocrine tumors.
abstract: BACKGROUND
  Compounds targeting somatostatin-receptor-type-2 (SSTR2) are useful for small bowel neuroendocrine tumor (SBNET) and pancreatic neuroendocrine tumor (PNET) imaging and treatment. We recently characterized expression of 13 cell surface receptor genes in SBNETs and PNETs, identifying three drug targets (GIPR, OXTR, and OPRK1). This study set out to characterize expression of this gene panel in the less common neuroendocrine tumors of the stomach and duodenum (gastric and duodenal neuroendocrine tumors [GDNETs]).
  
  
  METHODS
  Primary tumors and adjacent normal tissue were collected at surgery, RNA was extracted, and expression of 13 target genes was determined by quantitative polymerase chain reaction. Expression was normalized to GAPDH and POLR2A internal control genes. Expression relative to normal tissue (ddCT) and absolute expression (dCT) were calculated. Wilcoxon tests compared median expression with false discovery rate correction for multiple comparisons.
  
  
  RESULTS
  Gene expression was similar in two gastric and seven duodenal tumors, and these were analyzed together. Like SBNETs (n = 63) and PNETs (n = 51), GDNETs showed significant overexpression compared with normal tissue of BRS3, GIPR, GRM1, GPR113, OPRK1, and SSTR2 (P < 0.05 for all). Of these, SSTR2 had the highest absolute expression in GDNETs (median dCT 4.0). Absolute expression of BRS3, GRM1, GPR113, and OPRK1 was significantly lower than SSTR2 in GDNETs (P < 0.05 for all), whereas expression of GIPR was similar to SSTR2 (median 4.3, P = 0.4).
  
  
  CONCLUSIONS
  As in SBNETs and PNETs, GIPR shows absolute expression close to SSTR2 but has greater overexpression relative to normal tissue (21.1 versus 3.5-fold overexpression). We conclude that GIPR could provide an improved signal-to-noise ratio for imaging versus SSTR2 and represents a promising novel therapeutic target in GDNETs.
authors.affiliation: Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Scott K
authors.initials: SK
authors.lastname: Sherman
authors.affiliation: Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Maxwell
authors.affiliation: Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Carr
authors.affiliation: Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Donghong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: M Sue
authors.initials: MS
authors.lastname: O'Dorisio
authors.affiliation: Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: O'Dorisio
authors.affiliation: Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa. Electronic address: james-howe@uiowa.edu.
authors.forename: James R
authors.initials: JR
authors.lastname: Howe
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D004379:Duodenal Neoplasms / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000235:genetics*; D011964:Receptors, Gastrointestinal Hormone / Q000096:biosynthesis / Q000235:genetics*; D017481:Receptors, Somatostatin / Q000096:biosynthesis / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D011964:Receptors, Gastrointestinal Hormone; D017481:Receptors, Somatostatin; C574734:SSTR2 protein, human; C041086:gastric inhibitory polypeptide receptor
keywords: Duodenal; GIPR; Gastric; Gastric inhibitory polypeptide receptor; Gene expression; Neuroendocrine tumors; Octreotide; Pancreatic; Small bowel; Somatostatin receptor