Degree
Doctor of Philosophy (PhD)
Department
Veterinary Clinical Sciences
Document Type
Dissertation
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer in humans and domestic dogs. Despite extensive research, the mechanisms that drive HCC carcinogenesis and perpetuate cancer survival are incompletely understood in both species. The work described herein focused on finding similarities between canine and human HCC, which could be harnessed to benefit humans and dogs with cancer. The first aim was to investigate the expression of phosphoglycerate mutase 5 (PGAM5) in canine HCC. Upregulation of PGAM5 is a negative prognostic indicator in human HCC. Using archival formalin-fixed paraffin-embedded samples, we found that PGAM5 was overexpressed in canine HCC (n = 37) compared to peritumoral tissue (n = 21, p < 0.0001) and normal liver (n = 12, p = 0.0306). Our second aim was to determine if schistosomiasis was a risk factor for HCC in dogs as it is in humans. The specific pathogenesis of fluke-induced cancer is an avid area of research. Using the Louisiana Animal Disease Diagnostic Laboratory database, we determined that infection with the canine schistosome, Heterobilharzia americana (0.5%, 15/3,014 positive cases per canine liver submissions), increased the odds of HCC by a factor of 6.25 (95% confidence interval [1.39, 28.2], p = 0.017) compared to dogs without Heterobilharzia infection. We subsequently performed a prospective study to define the regional infection rate of asymptomatic dogs and found that H. americana was identified in 0.9% (1/111) of dogs. Because schistosome-induced cancer has been correlated to alterations in the liver immune microenvironment in humans, we optimized RNAscope to label H. americana in histology samples. This tool will be used to study the immunophenotype of canine schistosomiasis.
Date
7-9-2024
Recommended Citation
Devora, Priscilla, "Canine Hepatocellular Carcinoma: Evaluating PGAM5 and Heterobilharzia americana" (2024). LSU Doctoral Dissertations. 6512.
https://repository.lsu.edu/gradschool_dissertations/6512
Committee Chair
Johnston, Andrea
DOI
https://repository.lsu.edu/gradschool_dissertations/6512