Gastric inhibitory polypeptide receptor (GIPR) is a promising target for imaging and therapy in neuroendocrine tumors.
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.


CONCLUSIONS
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.
Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA.
Scott K
SK
Sherman
Jennifer C
JC
Carr
Donghong
D
Wang
M Sue
MS
O'Dorisio
Thomas M
TM
O'Dorisio
James R
JR
Howe
D014408:Biomarkers, Tumor / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D007414:Intestinal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D008024:Ligands; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D059906:Neuroimaging; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D012334:RNA, Neoplasm / Q000235:genetics; D018004:Receptors, Bombesin / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics*; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics; D017473:Receptors, Opioid, kappa / Q000235:genetics; D018045:Receptors, Oxytocin / Q000235:genetics; D017481:Receptors, Somatostatin / Q000235:genetics
C417525:ADGRV1 protein, human; D014408:Biomarkers, Tumor; D008024:Ligands; C515653:OPRK1 protein, human; C569600:OXTR protein, human; D012334:RNA, Neoplasm; D018004:Receptors, Bombesin; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; D018094:Receptors, Metabotropic Glutamate; D017473:Receptors, Opioid, kappa; D018045:Receptors, Oxytocin; D017481:Receptors, Somatostatin; C574734:SSTR2 protein, human; C107120:bombesin receptor subtype 3; C104077:metabotropic glutamate receptor type 1; C041086:gastric inhibitory polypeptide receptor