Changes in gene expression in small bowel neuroendocrine tumors associated with progression to metastases

Kendall J Keck; Patrick Breheny; Terry A Braun; Benjamin Darbro; Guiying Li; Joseph S Dillon; Andrew M Bellizzi; Thomas M O'Dorisio; James R Howe

doi:10.1016/j.surg.2017.07.031

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Changes in gene expression in small bowel neuroendocrine tumors associated with progression to metastases

Journal article

Open access

Peer reviewed

Changes in gene expression in small bowel neuroendocrine tumors associated with progression to metastases

Kendall J Keck, Patrick Breheny, Terry A Braun, Benjamin Darbro, Guiying Li, Joseph S Dillon, Andrew M Bellizzi, Thomas M O'Dorisio and James R Howe

Surgery, Vol.163(1), pp.232-239

01/2018

DOI: 10.1016/j.surg.2017.07.031

PMCID: PMC5736454

PMID: 29154080

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https://www.ncbi.nlm.nih.gov/pmc/articles/5736454View

Open Access

Abstract

Small bowel neuroendocrine tumors (SBNETs) present frequently with metastases, yet little is known about the molecular basis of this progression. This study sought to identify the serial differential expression of genes between normal small bowel, primary small bowel neuroendocrine tumors, and liver metastases. RNA isolated from matched normal small bowel tissue, primary small bowel neuroendocrine tumors, and liver metastases in 12 patients was analyzed with whole transcriptome expression microarrays and RNA-Seq. Changes in gene expression between primary small bowel neuroendocrine tumors and normal small bowels, and liver metastases versus primary small bowel neuroendocrine tumors were calculated. Common genes that were differentially expressed serially (increasing or decreasing from normal small bowel to primary small bowel neuroendocrine tumors to liver metastases) were identified, and 10 were validated using qPCR. Use of 2 transcriptome platforms allowed for a robust discrimination of genes important in small bowel neuroendocrine tumors progression. Serial differential expression was validated in 7/10 genes, all of which had been described previously in abdominal cancers, and with several interacting with members of the AKT, MYC, or MAPK3 pathways. Liver metastases had consistent underexpression of PMP22, while high expression of SERPINA10 and SYT13 was characteristic of both pSBTs and liver metastases. Identification of the serial differential expression of genes from normal tissues to primary tumors to metastases lends insight into important pathways for SBNETs progression. Differential expression of various genes, including PMP22, SYT13 and SERPINA10, are associated with the progression of SBNETs and warrant further investigation.

Gene Expression

Serpins - metabolism

Neuroendocrine Tumors - metabolism

Humans

Intestinal Neoplasms - metabolism

Gene Expression Profiling

Intestinal Neoplasms - pathology

Synaptotagmins - metabolism

Neoplasm Metastasis

Sequence Analysis, RNA

Neuroendocrine Tumors - secondary

Myelin P2 Protein - metabolism

Liver Neoplasms - metabolism

Intestine, Small - metabolism

Liver Neoplasms - secondary

Details

Title: Subtitle: Changes in gene expression in small bowel neuroendocrine tumors associated with progression to metastases
Creators: Kendall J Keck - Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
Patrick Breheny - Department of Biostatistics, University of Iowa College of Public Health, Iowa City, IA
Terry A Braun - Department of Biomedical Engineering, University of Iowa College of Engineering, Iowa City, IA
Benjamin Darbro - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA
Guiying Li - Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
Joseph S Dillon - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA
Andrew M Bellizzi - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA
Thomas M O'Dorisio - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA
James R Howe - Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA. Electronic address: james-howe@uiowa.edu
Resource Type: Journal article
Publication Details: Surgery, Vol.163(1), pp.232-239
DOI: 10.1016/j.surg.2017.07.031
PMID: 29154080
PMCID: PMC5736454
NLM abbreviation: Surgery
ISSN: 0039-6060
eISSN: 1532-7361
Publisher: United States
Grant note: P30 CA086862 / NCI NIH HHS T32 CA148062 / NCI NIH HHS P50 CA174521 / NCI NIH HHS
Language: English
Date published: 01/2018
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Stead Family Department of Pediatrics; Pathology; Biostatistics; Medical Genetics and Genomics; Surgery; Internal Medicine
Record Identifier: 9983997442102771

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