Expression and prognostic significance of CTLA-4 in canine mast cell tumors

Abstract

Canine mast cell tumors (MCTs) are among the most common cutaneous neoplasms in dogs, exhibiting variable biological behavior ranging from benign to highly malignant. Immune checkpoint molecules such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) have gained significant attention for their role in tumor immune evasion and potential prognostic implications. The present study was undertaken to evaluate CTLA-4 expression in 30 canine MCTs through real-time polymerase chain reaction (RT-PCR), and to assess its association with tumor grade and prognostic relevance. Quantitative RT-PCR demonstrated a marked upregulation of CTLA-4 mRNA expression in grade III and high-grade tumors, as determined by Kruskal-Wallis (p≤0.05) and Mann-Whitney (p≤0.01) tests. The Kruskal-Wallis test also revealed a statistically significant difference (p≤0.05) in mean CTLA-4 gene expression between recurrence and alive groups, and between dead and alive groups, while no significant difference (p>0.05) was noted between recurrence and dead groups. Kaplan-Meier survival analysis showed a significant (p≤0.05) reduction in survival time among dogs with CTLA-4 overexpression indicating its potential role in tumor aggressiveness and immune evasion. The findings suggest that CTLA-4 may serve as a promising biomarker for prognostication and as a potential therapeutic target in canine MCTs.