Semester of Graduation

Spring 2025

Degree

Master of Science (MS)

Department

Veterinary Clinical Sciences

Document Type

Thesis

Abstract

Hepatobiliary neuroendocrine neoplasms (HBNENs) are uncommon tumors in people and dogs, and the limited understanding of their biologic behavior often poses a diagnostic and prognostic challenge in the clinical setting. Though only a low number of cases have been described in dogs, there is evidence to indicate that primary gallbladder NENs may carry a more favorable prognosis compared to primary hepatic NENs. The emergence of liquid chromatography-mass spectrometry (LC-MS) in proteomic analysis has permitted large-scale analysis of neoplastic proteomes, allowing for better understanding of tumor pathophysiology while simultaneously enabling the rapid identification of protein biomarkers. Previous work in our laboratory compared the proteomic signature of canine hepatobiliary neuroendocrine neoplasms to that of normal hepatobiliary tissue, resulting in the identification of thirty-two differentially upregulated proteins. The goals of this study were to determine whether there is divergent protein expression in canine gallbladder versus hepatic NENs, and to further investigate HBNEN expression of three upregulated proteins of interest: transgelin, desmin, and galectin-1. Formalin-fixed paraffin embedded tissue from histologically confirmed canine primary hepatic (N = 10) and gallbladder (N = 24) NENs were submitted for LC-MS and bioinformatic analysis. Tissue expression of select proteins of interest was further evaluated by immunofluorescent labeling, as well as through RNA extraction and quantitative PCR (qPCR). The results of this study demonstrate distinct profiles of protein expression by canine hepatic and GB NENs, providing insight into the prognostic discrepancy between these tumor types. Additionally, the consistent positive immunolabeling of GB NENs for transgelin and galectin-1 serve as further validation of these proteins as prospective biomarkers in this tumor type. Further studies are needed to clarify the role of desmin in canine HBNENs.

Date

4-24-2025

Committee Chair

Johnston, Andrea

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