Network-Based Identification of Molecular Drivers and Therapeutic Targets in Canine Osteosarcoma
Elham Yekzaman,1Seyed amir hossein hosseini raviz,2,*
1. Department of Clinical Science, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman 2. Department of Clinical Science, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman
Introduction: Canine osteosarcoma is a clinically aggressive bone tumor that shares significant molecular and pathological similarities with human osteosarcoma, making it an excellent model for comparative oncology. In this study, we aimed to identify key molecular drivers and therapeutic targets by analyzing gene expression changes and protein interaction networks in canine osteosarcoma samples.
Methods: Two publicly available gene expression datasets containing both normal and osteosarcoma tumor samples from dogs were selected for analysis. Differentially expressed genes (DEGs) were identified using standard statistical approaches, followed by fold change filtering (thresholds >1 and <–1). To understand the functional context of these DEGs, we constructed a protein-protein interaction (PPI) network using the STRING database. The network was further analyzed in Cytoscape to identify subnetworks and central hub genes.
Results: Key hub genes identified included CDC20, PBK, KIF11, TTK, BUB1B, SGO1, RRM2, MKI67, CEP55, DEPDC1, CDK1, CCNA2, and mitochondrial-related genes such as NDUFS2, UQCRFS1, NDUFS7, NDUFS8, NDUFV1, NDUFB10, DCK, BLVRB, NDUFB2, MYL1, UQCRC1, and NDUFA9. Gene Ontology analysis revealed their involvement in essential biological processes such as cell cycle regulation, mitosis, checkpoint control, and protein ubiquitination, as well as oxidative phosphorylation and mitochondrial energy metabolism. Several genes were also linked to neurodegenerative and cancer-related signaling pathways, particularly those mediated by Rho GTPases.
Conclusion: Our integrative transcriptomic and network-based approach uncovered critical hub genes and pathways potentially driving the progression of canine osteosarcoma. The strong overlap of these mechanisms with those known in human cancers highlights the translational value of canine models in cancer research. These findings offer promising candidates for future gene-based therapies and biomarker development in both veterinary and human oncology.