Molecular Insights Into Canine Hepatocellular Carcinoma: A Cross-Species Transcriptomic Comparison With Human HCC

Canine hepatocellular carcinoma (HCC) requires further molecular characterization to identify diagnostic and therapeutic targets, and to establish whether dogs with this condition can model the human disease. Accordingly, we aimed to identify differentially expressed genes (DEGs) in canine HCC and evaluate cross-species transcriptomic dysregulation in canine and human HCC. Liver tissue samples from three dogs with HCC and three healthy dogs were subjected to next-generation sequencing, followed by RT-qPCR validation. Identified DEGs were then targeted in bioinformatics analyses (pathway enrichment, protein-protein interaction network, and hub gene analyses) for molecular characterization and comparison with human HCC datasets. We identified 975 DEGs (upregulated: 604; and downregulated: 371). Extracellular matrix-receptor interaction, focal adhesion, cell adhesion molecule, PI3K/Akt signaling, and cytokine/chemokine-related pathways were enriched. C1R, APOC3, C1QA, APOA1, C1QB, ACTG1, C1QC, CRP, ANXA5, and ANXA2 were identified as hub genes. Canine and human HCCs share 118 DEGs, highlighting conserved alterations in metabolic pathways, PI3K-Akt signaling, focal adhesion, and PPAR signaling pathways. Based on human HCC data, SPP1, NQO1, RRM2, APOA1, APOC3, ALDOB, and IGF1 were identified as prognosticators indicating poor overall survival. This study presents the first cross-species transcriptomic analysis of canine HCC, revealing significant molecular resemblances to human HCC, indicating it may be a promising comparative model for studying tumor biology, drug responses, and novel therapeutic interventions.