Erythrocyte membrane lipidomic signatures in canine lymphoma: immunophenotype-specific alterations and prognostic associations

Lipid metabolic dysregulation is increasingly recognized as a hallmark of cancer. Erythrocyte membrane fatty-acid (FA) profiling may reflect systemic metabolic alterations and provide non-invasive biomarkers of tumor biology. This prospective study investigated the erythrocyte membrane lipidomic profile of dogs with lymphoma and its potential prognostic relevance. Thirty-nine dogs with newly diagnosed lymphoma were enrolled. Clinical staging, flow-cytometric immunophenotyping, and erythrocyte membrane FA analysis were performed at diagnosis. Individual FAs, FA classes, and lipid-derived indices were compared between B-cell and T-cell lymphomas. Lymphoma-specific survival (LSS) was evaluated using Kaplan–Meier analysis and exploratory univariate Cox proportional hazards models. Twenty-five dogs had B-cell lymphoma, and 14 had T-cell lymphoma. T-cell lymphomas were more frequently extranodal, whereas B-cell lymphomas were predominantly multicentric. Palmitoleic acid was significantly lower in T-cell than in B-cell lymphoma. Correlation analysis revealed distinct lipidomic interaction patterns in dogs with lymphoma compared with healthy controls, particularly involving polyunsaturated fatty acids, omega-6 fatty acids, arachidonic acid, and the unsaturation index. The estimated LSS probability was approximately 50% at 180 days. Exploratory Cox analyses identified nominal associations between mixed diet and a lower hazard of lymphoma-related death, higher oleic acid concentrations and a lower hazard, and higher cis-vaccenic acid concentrations and a higher hazard. These findings should be interpreted with caution given the limited sample size, multiple comparisons, and lack of multivariable adjustment. Overall, erythrocyte membrane FA profiling identified immunophenotype-related differences and exploratory associations with outcome, supporting further investigation of lipidomics as a potential prognostic tool in canine lymphoma.