Abstract
BACKGROUND: The mechanisms underlying the development and prognosis of hepatocellular carcinoma (HCC) differ between dogs and humans. Although genetic alterations can cause carcinogenesis, the genetic alterations in canine HCC may differ from those observed in human HCC. In humans, various signaling pathways, oncogenes, and tumor suppressor genes are associated with HCC oncogenesis. Immune cells have been reported to be associated with prognosis. In canine HCC, the genes related to oncogenesis and prognosis remain unclear. Therefore, in this study, we used RNA sequencing to comprehensively evaluate abnormally expressed genes and infer immune cell composition in canine HCC. RESULTS: Fourteen dogs histopathologically diagnosed with HCC and four dogs with normal livers (NL) were included in this study. No HCC recurrence or metastasis was observed. A total of 260 differentially expressed genes were identified in dogs with HCC compared to those in NL dogs. Among them, 119 were downregulated and 141 were upregulated in HCC. Among the ontology and oncogenic signature gene sets, PRC1, CDCA3, and CDC20 were upregulated in the top 20 genes. Regulatory T cells (Treg) levels were decreased in the livers of dogs with HCC compared to those in normal livers. CONCLUSIONS: PRC1, CDCA3, and CDC20 were upregulated and were identified as candidate oncogenic genes in canine massive HCC. Downregulation of Tregs may be associated with prognosis in canine massive HCC.