Serum Redox Biomarkers in Canine Mast Cell Tumors: Exploratory Associations with Proliferative Activity and Clinicopathological Features

Abstract

Canine mast cell tumors (MCTs) exhibit heterogeneous biological behavior and provide a clinically relevant setting in which relationships between tumor phenotype and systemic redox homeostasis can be investigated. This exploratory prospective cohort study evaluated complementary circulating redox-related biomarkers representing hydroperoxide-derived oxidant products, antioxidant capacity, lipid peroxidation-related products, and oxidative DNA damage, and examined their associations with clinicopathological features of canine MCTs. Sixty-seven dogs with cytologically and histologically confirmed cutaneous or subcutaneous MCTs were included. Clinical staging was performed using cytological evaluation of lymph nodes, liver and spleen, and excised tumors were classified according to the Patnaik and Kiupel systems. Proliferative activity was assessed using Ki-67, and surgically excised lymph nodes were classified according to the Weishaar HN system. Serum reactive oxygen metabolites (d-ROMs), malondialdehyde (MDA), 8-hydroxy-2′-deoxyguanosine (8-OHdG) and antioxidant capacity using the OXY-adsorbent test were measured before therapeutic intervention. In the unadjusted analysis, serum MDA concentrations were higher in dogs with Ki-67 >23 than in dogs with Ki-67 ≤23 (median 10.8 vs. 7.0 μmol/L; raw p = 0.0254); however, this comparison did not remain statistically significant after Bonferroni correction for the 12 formal inferential biomarker × clinicopathological comparisons (adjusted p = 0.3052). The estimated Hodges–Lehmann location shift was +3.00 μmol/L (unadjusted bootstrap 95% CI, 0.58–6.00). No evaluated biomarker–clinicopathological association remained statistically significant after multiplicity adjustment. The observed MDA–Ki-67 pattern should therefore be regarded as exploratory and hypothesis-generating rather than as evidence of established prognostic or clinical utility. Long-term data on recurrence, progression, and survival were not available; therefore, prognostic utility could not be evaluated. Larger prospective studies incorporating longitudinal outcomes are warranted.