Comparative Multi-Omics Evaluation of the Tumor Microenvironment in Canine and Human Hepatocellular Carcinoma

This distinction offers a unique comparative perspective on the intrinsic genetic drivers of the disease.

Methods

Using whole exome sequencing (WES) and single nucleus RNA sequencing (snRNA-seq) in tandem, we perform a multi-omic analysis of the dog HCC tumor. Results: Mutational analysis of impactful polymorphisms revealed a conserved cross-species landscape with genes such as CTNNB1, known for highly recurrent mutations in human HCC, showing similar alterations in dogs. In dog HCC tumors, we identified major cell types commonly observed in human HCC, including T lymphocyte, endothelial, macrophage, fibroblast, hepatocyte, malignant, and non-specific proliferating types.

A comparative analysis of intercellular interactions across human and dog HCC cell types revealed intriguing parallels, particularly in macrophage functionality. Conclusions: These findings underscore the need for expanded genetic studies of dog HCC to further elucidate cross-species commonalities, offering deeper insights into key aspects of HCC biology and identifying novel therapeutic targets.