Transcriptomic signatures of cytomorphological heterogeneity in canine transmissible venereal tumor.

Abstract

BACKGROUND: Canine transmissible venereal tumor (CTVT) is a naturally occurring, clonally transmissible cancer that persists in hosts through mechanisms of immune evasion and adaptation. It presents three cytomorphological subtypes-plasmacytoid, lymphocytoid, and mixed-each linked to distinct clinical behaviors and therapeutic responses. These phenotypes likely reflect divergent transcriptional programs, but their molecular basis remains poorly defined. OBJECTIVE: This study aimed to describe transcriptional profiles associated with CTVT subtypes and identify pathways underlying their biological behaviors. METHODS: We analyzed RNA-Seq data from 10 CTVT tumors classified into plasmacytoid, lymphocytoid, and mixed subtypes. Differential expression analysis was conducted using DESeq2, followed by functional enrichment (DAVID), protein-protein interaction analysis (STRING), and co-expression network construction with Pearson correlation and Louvain clustering. RESULTS: The strongest transcriptional divergence was observed between plasmacytoid and lymphocytoid subtypes, with 237 differentially expressed genes enriched in immune pathways. Plasmacytoid tumors showed upregulation of immune-related genes, including CXCL10, IL15, CD74, and DLA-DQA1, forming MHC-II co-expression modules. Lymphocytoid tumors upregulated genes involved in DNA repair and proliferation, such as ATM, PCBP1, and CDK1. Comparisons with the mixed subtype revealed fewer DEGs and limited enrichment, suggesting an intermediate transcriptional profile. CONCLUSIONS: Our findings reveal subtype-specific transcriptional programs in CTVT. The plasmacytoid subtype displayed enriched immune signatures, particularly in antigen presentation and cytokine signaling, while the lymphocytoid subtype showed a proliferative, immune-silent profile. Mixed tumors exhibited intermediate or transitional features. These insights support a molecular taxonomy of CTVT and highlight potential biomarkers for future prognostic and therapeutic stratification.