Journal article
Gene expression accurately distinguishes liver metastases of small bowel and pancreas neuroendocrine tumors
Clinical & experimental metastasis, Vol.31(8), pp.935-944
12/2014
DOI: 10.1007/s10585-014-9681-2
PMCID: PMC4263419
PMID: 25241033
Abstract
Small bowel (SBNETs) and pancreatic neuroendocrine tumors (PNETs) often present with liver metastases. Although liver biopsy establishes a neuroendocrine diagnosis, the primary tumor site is frequently unknown without exploratory surgery. Gene expression differences in metastases may distinguish primary SBNETs and PNETs. This study sought to determine expression differences of four genes in neuroendocrine metastases and to create a gene expression algorithm to distinguish the primary site. Nodal and liver metastases from SBNETs and PNETs (n = 136) were collected at surgery under an Institutional Review Board-approved protocol. Quantitative PCR measured expression of bombesin-like receptor-3, opioid receptor kappa-1, oxytocin receptor, and secretin receptor in metastases. Logistic regression models defined an algorithm predicting the primary tumor site. Models were developed on a training set of 21 nodal metastases and performance was validated on an independent set of nodal and liver metastases. Expression of all four genes was significantly different in SBNET compared to PNET metastases. The optimal model employed expression of bombesin-like receptor-3 and opioid receptor kappa-1. When these genes did not amplify, the algorithm used oxytocin receptor and secretin receptor expression, which allowed classification of all 136 metastases with 94.1 % accuracy. In the independent liver metastasis validation set, 52/56 (92.9 %) were correctly classified. Positive predictive values were 92.5 % for SBNETs and 93.8 % for PNETs. This validated algorithm accurately distinguishes SBNET and PNET metastases based on their expression of four genes. High accuracy in liver metastases demonstrates applicability to the clinical setting. Studies assessing this algorithm’s utility in prospective clinical decision-making are warranted.
Details
- Title: Subtitle
- Gene expression accurately distinguishes liver metastases of small bowel and pancreas neuroendocrine tumors
- Creators
- Scott Sherman - Department of Surgery The University of Iowa Carver College of Medicine 200 Hawkins Drive Iowa City IA 52242-1086 USAJessica Maxwell - Department of Surgery The University of Iowa Carver College of Medicine 200 Hawkins Drive Iowa City IA 52242-1086 USAJennifer Carr - Department of Surgery The University of Iowa Carver College of Medicine 200 Hawkins Drive Iowa City IA 52242-1086 USADonghong Wang - Department of Surgery The University of Iowa Carver College of Medicine 200 Hawkins Drive Iowa City IA 52242-1086 USAAndrew Bellizzi - Department of Pathology The University of Iowa Carver College of Medicine 200 Hawkins Drive Iowa City IA 52242 USAM. Sue O'Dorisio - Department of Pediatrics The University of Iowa Carver College of Medicine 200 Hawkins Drive Iowa City IA 52242 USAThomas O’Dorisio - Department of Internal Medicine The University of Iowa Carver College of Medicine 200 Hawkins Drive Iowa City 52242 IA USAJames Howe - Department of Surgery The University of Iowa Carver College of Medicine 200 Hawkins Drive Iowa City IA 52242-1086 USA
- Resource Type
- Journal article
- Publication Details
- Clinical & experimental metastasis, Vol.31(8), pp.935-944
- DOI
- 10.1007/s10585-014-9681-2
- PMID
- 25241033
- PMCID
- PMC4263419
- NLM abbreviation
- Clin Exp Metastasis
- ISSN
- 0262-0898
- eISSN
- 1573-7276
- Publisher
- Springer Netherlands; Dordrecht
- Language
- English
- Date published
- 12/2014
- Academic Unit
- Stead Family Department of Pediatrics; Pathology; Surgery; Endocrinology and Metabolism; Otolaryngology; Internal Medicine
- Record Identifier
- 9984046801202771
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