BACKGROUND: Ligands binding the somatostatin receptor type 2 (SSTR2) are useful for imaging and treatment of neuroendocrine tumors (NETs), but not all tumors express high levels of these receptors. The aim of this study was to evaluate gene expression of new therapeutic targets in NETs relative to SSTR2. METHODS: RNA was extracted from 103 primary small bowel and pancreatic NETs, matched normal tissue, and 123 metastases. Expression of 12 candidate genes was measured by quantitative polymerase chain reaction normalized to internal controls; candidate gene expression was compared with SSTR2. RESULTS: Relative to normal tissue, primary NET expression of SSTR2, GPR98, BRS3, GIPR, GRM1, and OPRK1 were increased by 3, 8, 13, 13, 17, and 20-fold, respectively. Similar changes were found in metastases. Although most candidate genes showed lesser absolute expressions than SSTR2, absolute GIPR expression was closest to SSTR2 (mean dCT 3.6 vs. 2.7, P = .01). Absolute OPRK1 and OXTR expression varied greatly by primary tumor type and was close to SSTR2 in small bowel NETs but not pancreatic NETs. CONCLUSION: Compared with the current treatment standard SSTR2, GIPR has only somewhat lesser absolute gene expression in tumor tissue but much lesser expression in normal tissue, making it a promising new target for NET imaging and therapy.
BACKGROUND: Ligands binding the somatostatin receptor type 2 (SSTR2) are useful for imaging and treatment of neuroendocrine tumors (NETs), but not all tumors express high levels of these receptors. The aim of this study was to evaluate gene expression of new therapeutic targets in NETs relative to SSTR2. METHODS: RNA was extracted from 103 primary small bowel and pancreatic NETs, matched normal tissue, and 123 metastases. Expression of 12 candidate genes was measured by quantitative polymerase chain reaction normalized to internal controls; candidate gene expression was compared with SSTR2. RESULTS: Relative to normal tissue, primary NET expression of SSTR2, GPR98, BRS3, GIPR, GRM1, and OPRK1 were increased by 3, 8, 13, 13, 17, and 20-fold, respectively. Similar changes were found in metastases. Although most candidate genes showed lesser absolute expressions than SSTR2, absolute GIPR expression was closest to SSTR2 (mean dCT 3.6 vs. 2.7, P = .01). Absolute OPRK1 and OXTR expression varied greatly by primary tumor type and was close to SSTR2 in small bowel NETs but not pancreatic NETs. CONCLUSION: Compared with the current treatment standard SSTR2, GIPR has only somewhat lesser absolute gene expression in tumor tissue but much lesser expression in normal tissue, making it a promising new target for NET imaging and therapy.
Authors: Skye C Mayo; Mechteld C de Jong; Carlo Pulitano; Brian M Clary; Srinevas K Reddy; T Clark Gamblin; Scott A Celinksi; David A Kooby; Charles A Staley; Jayme B Stokes; Carrie K Chu; Alessandro Ferrero; Richard D Schulick; Michael A Choti; Giles Mentha; Jennifer Strub; Todd W Bauer; Reid B Adams; Luca Aldrighetti; Lorenzo Capussotti; Timothy M Pawlik Journal: Ann Surg Oncol Date: 2010-06-29 Impact factor: 5.344
Authors: Fadi S Dahdaleh; Daniel Calva-Cerqueira; Jennifer C Carr; Junlin Liao; James J Mezhir; Thomas M O'Dorisio; James R Howe Journal: Ann Surg Oncol Date: 2011-08-16 Impact factor: 5.344
Authors: L Bodei; J Mueller-Brand; R P Baum; M E Pavel; D Hörsch; M S O'Dorisio; T M O'Dorisio; T M O'Dorisiol; J R Howe; M Cremonesi; D J Kwekkeboom; John J Zaknun Journal: Eur J Nucl Med Mol Imaging Date: 2013-05 Impact factor: 9.236
Authors: Jennifer C Carr; Erin A Boese; Philip M Spanheimer; Fadi S Dahdaleh; Molly Martin; Daniel Calva; Blanca Schafer; David M Thole; Terry Braun; Thomas M O'Dorisio; M Sue O'Dorisio; James R Howe Journal: Surgery Date: 2012-12 Impact factor: 3.982
Authors: N Kuzumaki; A Suzuki; M Narita; T Hosoya; A Nagasawa; S Imai; K Yamamizu; H Morita; H Nagase; Y Okada; H J Okano; J K Yamashita; H Okano; T Suzuki; M Narita Journal: Br J Cancer Date: 2012-02-16 Impact factor: 7.640
Authors: Scott K Sherman; Jessica E Maxwell; M Sue O'Dorisio; Thomas M O'Dorisio; James R Howe Journal: Ann Surg Oncol Date: 2014-04-22 Impact factor: 5.344
Authors: Jessica E Maxwell; Scott K Sherman; Kristen M Stashek; Thomas M O'Dorisio; Andrew M Bellizzi; James R Howe Journal: Surgery Date: 2014-11-11 Impact factor: 3.982
Authors: Scott K Sherman; Jessica E Maxwell; Jennifer C Carr; Donghong Wang; M Sue O'Dorisio; Thomas M O'Dorisio; James R Howe Journal: J Surg Res Date: 2014-01-29 Impact factor: 2.192
Authors: Scott K Sherman; Jessica E Maxwell; Jennifer C Carr; Donghong Wang; Andrew M Bellizzi; M Sue O'Dorisio; Thomas M O'Dorisio; James R Howe Journal: Clin Exp Metastasis Date: 2014-09-21 Impact factor: 5.150