Thymidine kinase 1 as a diagnostic tumor marker is of moderate value in cancer patients: A meta‑analysis

TK1 ENGINEERED CELLS

ABSTRACT

Thymidine kinase 1 (TK1) is an enzyme involved in nucleic acid synthesis and is therefore considered to be an important tumor proliferation marker. The aim of the present study was to determine the diagnostic role of TK1 measurement in cancer. An extensive electronic search was performed in PubMed, EMBASE and the Cochrane Library using the keywords ‘thymidine kinase 1’ and ‘tumor’ and synonyms. This study was conducted as part of a project to establish evidencebased guidelines for the diagnosis and treatment of cancer. A total of 453 abstracts were screened, after which the full text of 40 studies were selected for further investigation, including screening of the references cited by studies in the original search. Fifteen studies were enrolled following fulltext evaluation. The areas under the receiver operating characteristic curves for the radioenzymatic assay (REA), the chemiluminescence immunoassay (CLIA) and the total were 0.88, 0.75 and 0.8, respectively. These results were all between <0.9 and >0.7, which suggested a moderate diagnostic efficacy. The positive likelihood ratio of the CLIA method was the highest (10.229), which demonstrated that CLIA exhibited a satisfactory specificity in tumor diagnosis. However, TK1 as a single diagnostic tumor marker was not of significant value and the combination of more tumor markers in the diagnosis of tumors may be preferable.

INTRODUCTION

Malignant tumors are characterized by uncontrolled cell proliferation. The proliferative activity of neoplastic cells is key to the clinical course of several neoplasms (13). Thus, indicators of proliferation are attractive candidates as prognostic markers. Among these, thymidine kinase 1 (TK1), a cellular enzyme involved in a salvage pathway for DNA synthesis, has attracted interest. TK1 is located at chromosome 17q25, is exclusively expressed in the cytoplasm of dividing cells and is absent in resting cells (47). TK1 activity increases during the G1̸S phase and decreases through the G2̸mitosis phase (810). TK1 activity is essential for the balance of the intracellular TTP levels. In the beginning of G1 the cellular concentration of TK1 is not measurable. Transcriptional and translational mechanisms control the increased expression in the early S phase (1114). Its activity has been shown to be correlated with the proliferative activity of tumor cells. Therefore, it may be useful for the early detection of tumor cell division and proliferation.

The appearance of TK1 in the serum results from tumor cell death by disintegration and it may be correlated with the size of the tumor, as a larger tumor contains more TK1 compared to a smaller one. TK1 has been extensively studied, primarily as a diagnostic biomarker for a variety of cancer types. The first assay for TK detection was developed by Gronowitz and Kallander (15). As a biomarker, higher serum TK1 activity levels are correlated with a more advanced cancer stage and grade (16). Serum TK1 levels also show prognostic potential, as they may help predict future relapse at the time of primary diagnosis in several cancer patients, including those with solid and nonsolid tumors.

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