Abstract
BackgroundThymidine kinase 1 (TK1) catalyzes the initial phosphorylation of thymidine in the salvage pathway synthesis of dTTP, an essential building block of DNA. TK1 is a cytosolic enzyme with its highest level during the S-phase of the cell cycle. In cancer cells TK1 is upregulated and excess TK1 is leaked into the blood. Therefore, serum TK1 has been used as biomarker for cancer diagnosis and prognosis in human medicine. Feline TK1 shows high sequence similarity to TK1 from other species. The aim of this study was to characterize feline TK1 and evaluate if serum TK1 can be used as a diagnostic biomarker.ResultsFeline TK1 was cloned, expressed and affinity purified. The purified feline TK1 phosphorylated not only pyrimidine deoxyribonucleosides but also pyrimidine ribonucleosides and to some extent purine deoxynucleosides. A number of anticancer and antiviral nucleoside analogs also served as substrates with fairly high efficiency. ATP and dATP were the preferred phosphate donor. Serum TK1 activity in felines with malignant diseases was significantly higher than that in healthy individuals. ROC analysis revealed an area under the curve (AUC) of 0.98 with a sensitivity of 0.83 and a specificity of 0.95 for felines with lymphoma. Serum TK1 activity in felines with IBD or inflammatory disease was within the same range as healthy ones. Furthermore, in felines with lymphoma serum TK1 activity returned to normal levels in response to treatment.ConclusionFeline TK1 has high specific activity and a broader substrate specificity in comparison with TK1 from other species. Serum TK1 activity in felines with malignant diseases is significantly higher than that in normal felines and in felines with inflammatory diseases. These results suggest that serum TK1 may be a promising biomarker for the diagnosis and monitoring of malignant diseases and for the differential diagnosis of certain inflammatory disease.
Highlights
Thymidine kinase 1 (TK1) catalyzes the initial phosphorylation of thymidine in the salvage pathway synthesis of dTTP, an essential building block of DNA
The aim of this study was to conduct a biochemical characterization of feline TK1 and to evaluate if serum TK1 can be used as a biomarker in clinical diagnostics
We showed here that serum TK1 activity in felines with Inflammatory bowel disease (IBD) or inflammatory disease was in the same range as normal individuals, albeit a small number of samples were included in this study
Summary
Thymidine kinase 1 (TK1) catalyzes the initial phosphorylation of thymidine in the salvage pathway synthesis of dTTP, an essential building block of DNA. Serum TK1 has been used as biomarker for cancer diagnosis and prognosis in human medicine. The aim of this study was to characterize feline TK1 and evaluate if serum TK1 can be used as a diagnostic biomarker. Wang et al BMC Vet Res (2021) 17:316 medicine, serum TK1 has been used in health screening and for cancer diagnosis and prognosis [6, 7]. Serum TK1 have been evaluated as biomarker for diagnosis and prognosis primarily in canines with hematological malignancies [8,9,10]. Lymphoma is the most common neoplastic disease in felines, accounting for approximately 30% of all cancer cases. Up to 55% are alimentary lymphoma [11, 12], which is characterized by neoplastic lymphocyte infiltration of the gastrointestinal tract and/or associated lymph nodes. In cases of low grade alimentary lymphoma histological assessment of biopsies is required, whereas intermediate and high grade alimentary lymphoma can be diagnosed by cytology of intestinal or mesenteric lymph node aspirates using fine needle aspiration [11, 12]
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