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Feline thymidine kinase 1: molecular characterization and evaluation of its serum form as a diagnostic biomarker

Wang, Liya and Sharif, Hanan and Saellström, Sara and Rönnberg, Henrik and Eriksson, Staffan (2021). Feline thymidine kinase 1: molecular characterization and evaluation of its serum form as a diagnostic biomarker. BMC Veterinary Research. 17 , 316
[Research article]

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Abstract

Background Thymidine 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. Results Feline 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. Conclusion Feline 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.

Authors/Creators:Wang, Liya and Sharif, Hanan and Saellström, Sara and Rönnberg, Henrik and Eriksson, Staffan
Title:Feline thymidine kinase 1: molecular characterization and evaluation of its serum form as a diagnostic biomarker
Series Name/Journal:BMC Veterinary Research
Year of publishing :2021
Volume:17
Article number:316
Number of Pages:10
Publisher:BMC
ISSN:1746-6148
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Clinical Science
Keywords:Feline thymidine kinase 1, Biomarkers, Feline lymphoma, Inflammatory diseases, Cancer diagnostics
URN:NBN:urn:nbn:se:slu:epsilon-p-113959
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-113959
Additional ID:
Type of IDID
DOI10.1186/s12917-021-03030-5
Web of Science (WoS)000700398600001
ID Code:25687
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
University Animal Hospital
Department:(VH) > Dept. of Anatomy, Physiology and Biochemistry
University Animal Hospital (UAH)
(VH) > Dept. of Clinical Sciences
Deposited By: SLUpub Connector
Deposited On:15 Oct 2021 12:25
Metadata Last Modified:15 Oct 2021 12:31

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