Differentiation of small bowel and pancreatic neuroendocrine tumors by gene-expression profiling

• Published in: Surgery Vol. 152; no. 6; pp. 998 - 1007
• Main Authors: Carr, Jennifer C., MD, Boese, Erin A., BA, Spanheimer, Philip M., MD, Dahdaleh, Fadi S., MD, Martin, Molly, PhD, Calva, Daniel, MD, Schafer, Blanca, MS, Thole, David M., BS, Braun, Terry, PhD, O'Dorisio, Thomas M., MD, O'Dorisio, M. Sue, MD, PhD, Howe, James R., MD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01-12-2012; Elsevier
• Subjects: Biological and medical sciences; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Profiling; General aspects; Humans; Intestinal Neoplasms - diagnosis; Intestinal Neoplasms - genetics; Intestinal Neoplasms - pathology; Intestine, Small; Liver Neoplasms - genetics; Liver Neoplasms - secondary; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Neuroendocrine Tumors - diagnosis; Neuroendocrine Tumors - genetics; Neuroendocrine Tumors - secondary; Pancreatic Neoplasms - diagnosis; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Receptors, G-Protein-Coupled - genetics; Surgery; Tumors; Digestive system; Malignant tumor; Cell differentiation; Small intestine; Gene expression profile; Pancreatic neuroendocrine tumor; Medicine; Treatment; Surgery; Digestive diseases; Differentiation; Cancer; Pancreatic disease
• ISSN: 0039-6060; 1532-7361
• DOI: 10.1016/j.surg.2012.08.040

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. Conclusion Differential expression patterns using as few as 2 to 4 GPCR genes successfully discriminated primary sites in small bowel and pancreatic NETs.