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INTERNATIONAL CONGRESS OF

CancerGenetics

• Identification of Molecular Targets for Gene Therapy in Canine Mammary Tumors Through Integrative Gene Network Analysis

• Seyed amir hossein hosseini raviz,¹ Elham yekzaman,^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 mammary tumors (CMTs) are the most prevalent neoplasms in female dogs and share significant biological and clinical features with human breast cancer. The exploration of their molecular landscape offers valuable insights into tumor development, progression, and treatment response. With the rising importance of gene and cell-based therapies in oncology, it is critical to identify specific molecular targets associated with CMTs. In this study, we employed bioinformatic analysis of gene expression data to uncover differentially expressed genes (DEGs) and functional pathways in canine mammary tumors. The ultimate goal was to highlight potential candidates for therapeutic intervention using gene or cell-based strategies.
• Methods: We selected two publicly available datasets containing both tumor and adjacent normal mammary tissue samples from dogs. Raw expression data were normalized to correct for technical variability. Differential expression analysis was performed using the Limma package in RStudio to identify DEGs, and a t-test was conducted in geWorkbench to obtain statistical significance in terms of p-values and log fold changes (logFC). Genes with |logFC| ≥ 1 and adjusted p-value < 0.05 were considered significantly differentially expressed. The DEGs were used to construct a protein-protein interaction (PPI) network via the STRING database. The resulting network was imported into Cytoscape software to identify sub-networks and hub genes based on topological analysis. These hub genes were then analyzed for functional enrichment using the DAVID platform to retrieve relevant Gene Ontology (GO) terms and pathway associations.
• Results: From the differential expression analysis, a set of significant DEGs was identified. Network analysis in Cytoscape highlighted several hub genes, including keratin-related genes (such as KRT82, KRT83, KRT25, KRT27, KRT18, KRT23, KRT36, and KRT26), hormone and extracellular matrix-related genes (SPP1, IGF1, PPARG, ACAN, and BGN), and key regulators of the cell cycle (CDK1, CCNA2, BUB1B, PLK1, TTK, PBK, KIF11, MELK, KIFC1, TPX2, NDC80, CDCA8, DEPDC1, and KIF15). Functional annotation revealed that these hub genes were enriched in several biological processes, including intermediate filament organization, keratinization, estrogen signaling, epithelial cell differentiation, and a broad spectrum of mitotic cell cycle activities. Signaling by RHO GTPases and processes related to spindle checkpoint and chromatid separation were also among the enriched pathways. These pathways are directly related to proliferation, differentiation, and structural remodeling, making them highly relevant in the context of cancer progression and therapeutic targeting.
• Conclusion: This integrative analysis of gene expression data in canine mammary tumors revealed a network of key genes and signaling pathways involved in tumor biology. The identified genes and enriched pathways are associated with essential oncogenic processes such as cell cycle regulation, hormone signaling, and cytoskeletal organization. These findings underscore the utility of CMT as a comparative model for breast cancer and highlight specific molecular targets for the development of gene- or cell-based therapeutic strategies. This work provides a foundation for future translational studies aimed at precision oncology in both veterinary and human medicine.
• Keywords: Canine mammary tumor, differential gene expression, gene network, gene therapy, hub genes