Potential of circulating microRNAs as biomarkers in veterinary medicine

Abstract

In humans, multiple cytokines have been linked to the development of lymphoma, and are relevant biomarkers for response to chemotherapy and prognosis. In contrast, only a few circulating cytokines have been studied in dogs with lymphoma. We prospectively enrolled thirty-one dogs newly diagnosed with multicentric lymphoma. Immunophenotype was determined by flow cytometry in all dogs, separating them into 2 subgroups: B cell lymphoma (n = 21) and T cell lymphoma (n = 10). Nineteen healthy dogs were enrolled in the control group. Circulating cytokine concentrations were measured using a commercial canine multiplex magnetic bead-based assay which included Interleukin-2 (IL-2), IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF), Tumor Necrosis Factor-α (TNF-α), Interferon γ (IFN-γ), IFN-γ induced Protein-10 (IP-10), Keratinocyte Chemoattractant-like (KC-like), and Monocyte Chemoattractant Protein-1 (MCP-1). The serum levels of each cytokine were first compared between the lymphoma and control groups, and then between the B cell lymphoma, T cell lymphoma, and control groups. There was no significant difference between the lymphoma and healthy control groups regarding sex, age and weight. MCP-1, IL-6, and IL-10 were significantly higher in dogs with lymphoma compared to healthy dogs (p < 0.01, p = 0.01 and p = 0.03, respectively). MCP-1 and IL-10 were significantly higher in the B cell lymphoma group than in the healthy group (p = 0.01, p = 0.01, respectively). MCP-1 and IL-6 levels were significantly higher in the T cell lymphoma group than in the healthy group (p = 0.02, p < 0.01, respectively). IL-6 was significantly higher in the T cell lymphoma group than in the B cell lymphoma group (p = 0.03). Significant differences among the groups were found for IL-15 and KC-like, but they were affected by age and/or sex. There were no significant differences in serum IL-2, IL-7, IL-8, IL-18, GM-CSF, TNF-α, IFN-γ, and IP-10 between any of the groups. Significant differences in red blood cell, white blood cell, neutrophil, lymphocyte and monocyte counts were also found between the different groups of dogs. Our data showed different serum cytokine and peripheral blood cell profiles between dogs with lymphoma and healthy dogs, and between dogs with B cell and T cell lymphoma. Further study is necessary to investigate the role of these cytokines in lymphoma pathogenesis, response to treatment, and prognosis, and the influence of age, sex and blood cell counts on their expression.