Pilot study on differential gene expression in relation to vincristine response in canine transmissible venereal tumor.

Abstract

BACKGROUND: The canine transmissible venereal tumor (CTVT) is a naturally occurring clonal cancer that offers a unique model to study tumor evolution, immune evasion, and chemoresistance. Although vincristine induces complete remission in most cases, some tumors show partial response or resistance, and the molecular drivers of this variability remain unclear. While genomic and epigenetic studies have implicated multidrug resistance and immune modulation, transcriptional mechanisms underlying therapeutic outcomes are not fully characterized. OBJECTIVE: To identify transcriptomic signatures and functional gene modules associated with vincristine response in CTVT showing complete response (CR), partial response (PR), or resistance (R). METHODS: We analyzed RNA-Seq data from 10 CTVT tumors grouped by therapeutic response. After filtering and quality control, differential expression was assessed using DESeq2. Functional enrichment was evaluated using DAVID, and protein-protein interaction networks were built with STRING. Co-expression modules were identified via Pearson correlation and Louvain clustering. RESULTS: We identified 97 DEGs (CR vs. R), 89 (PR vs. R), and 55 (CR vs. PR). Complete response tumors showed upregulation of immune-related (CD79A, CD19), extracellular matrix (ITGB3), and mitophagy genes (BCL2L13), while R tumors expressed markers of stress adaptation and resistance (GNG4, XPO1, KCNJ3). Partial response tumors displayed intermediate profiles (CSNK2B, DHX9). Protein-protein interaction networks showed limited connectivity, but co-expression modules revealed distinct expression patterns associated with response. CONCLUSION: This exploratory analysis characterizes transcriptional differences among response groups and identifies candidate genes and pathways that may contribute to vincristine sensitivity or resistance in CTVT. Considering the small number of resistant tumors included, these results are preliminary and require validation in larger, independent cohorts.