Scott K Sherman1, Jessica E Maxwell1, Jennifer C Carr1, Donghong Wang1, M Sue O'Dorisio2, Thomas M O'Dorisio3, James R Howe4. 1. Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa. 2. Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa. 3. Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa. 4. Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa. Electronic address: james-howe@uiowa.edu.
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.
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: P Jaïs; B Terris; P Ruszniewski; M LeRomancer; F Reyl-Desmars; C Vissuzaine; G Cadiot; M Mignon; M J Lewin Journal: Eur J Clin Invest Date: 1997-08 Impact factor: 4.686
Authors: A Lacroix; E Bolté; J Tremblay; J Dupré; P Poitras; H Fournier; J Garon; D Garrel; F Bayard; R Taillefer Journal: N Engl J Med Date: 1992-10-01 Impact factor: 91.245
Authors: Marianne Pavel; Eric Baudin; Anne Couvelard; Eric Krenning; Kjell Öberg; Thomas Steinmüller; Martin Anlauf; Bertram Wiedenmann; Ramon Salazar Journal: Neuroendocrinology Date: 2012-02-15 Impact factor: 4.914
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: James C Yao; Manal Hassan; Alexandria Phan; Cecile Dagohoy; Colleen Leary; Jeannette E Mares; Eddie K Abdalla; Jason B Fleming; Jean-Nicolas Vauthey; Asif Rashid; Douglas B Evans Journal: J Clin Oncol Date: 2008-06-20 Impact factor: 44.544
Authors: E P Krenning; D J Kwekkeboom; W H Bakker; W A Breeman; P P Kooij; H Y Oei; M van Hagen; P T Postema; M de Jong; J C Reubi Journal: Eur J Nucl Med Date: 1993-08
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: Oliver Kaut; Ina Schmitt; Andrea Hofmann; Per Hoffmann; Thomas E Schlaepfer; Ullrich Wüllner; René Hurlemann Journal: Eur Arch Psychiatry Clin Neurosci Date: 2015-01-09 Impact factor: 5.270
Authors: Yingnan Si; Seulhee Kim; Jianfa Ou; Yun Lu; Patrick Ernst; Kai Chen; Jason Whitt; Angela M Carter; James M Markert; James A Bibb; Herbert Chen; Lufang Zhou; Renata Jaskula-Sztul; Xiaoguang Margaret Liu Journal: Cancer Gene Ther Date: 2020-07-20 Impact factor: 5.987