title: Differentiation of small bowel and pancreatic neuroendocrine tumors by gene-expression profiling.
abstract: BACKGROUND
  Between 10% and 20% of patients with neuroendocrine tumors (NETs) present with metastases of unknown primary site. Because knowledge of the primary site has important implications for treatment, we set out to define gene-expression profiles to differentiate between small-bowel NETs (SBNETs) and pancreatic NETs (PNETs).
  
  
  METHODS
  RNA was extracted from tumor and normal tissues in 11 patients with SBNETs and 15 patients with PNETs, and qPCR was performed for 367 GPCR genes. Differentially expressed genes were identified using the RT2 Profiler. Whole genome expression analysis was performed on 11 SBNETs, 5 PNETS, and corresponding normal tissues. Statistical significance was evaluated by the Student t test and ANOVA.
  
  
  RESULTS
  Whole-genome analysis revealed 173 significantly differentially expressed genes in SBNETs and normal tissues and in 52 in PNETs. GPCR arrays identified 28 genes in SBNETs and 18 in PNETs, with significant expression differences from normal tissues. In all SBNETs, 2 genes were significantly upregulated by more than fivefold: OXTR and GPR113. No PNETs shared this profile, whereas 73% had a greater than fivefold downregulation of ADORA1 and SCTR. These genes also allowed for determination of the primary site in 8 of 10 liver metastases.
  
  
  CONCLUSIONS
  Differential expression patterns using as few as 2 to 4 GPCR genes successfully discriminated primary sites in small bowel and pancreatic NETs.
authors.affiliation: Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA 52242-1086, USA.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Carr
authors.forename: Erin A
authors.initials: EA
authors.lastname: Boese
authors.forename: Philip M
authors.initials: PM
authors.lastname: Spanheimer
authors.forename: Fadi S
authors.initials: FS
authors.lastname: Dahdaleh
authors.forename: Molly
authors.initials: M
authors.lastname: Martin
authors.forename: Daniel
authors.initials: D
authors.lastname: Calva
authors.forename: Blanca
authors.initials: B
authors.lastname: Schafer
authors.forename: David M
authors.initials: DM
authors.lastname: Thole
authors.forename: Terry
authors.initials: T
authors.lastname: Braun
authors.forename: Thomas M
authors.initials: TM
authors.lastname: O'Dorisio
authors.forename: M Sue
authors.initials: MS
authors.lastname: O'Dorisio
authors.forename: James R
authors.initials: JR
authors.lastname: Howe
mesh_terms: D020869:Gene Expression Profiling; D006801:Humans; D007414:Intestinal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D007421:Intestine, Small; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000235:genetics / Q000556:secondary; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*
chemical_list: D043562:Receptors, G-Protein-Coupled