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Research article2023Peer reviewedOpen access

A Dual Biomarker TK1 Protein and CA125 or HE4-Based Algorithm as a Better Diagnostic Tool than ROMA Index in Early Detection of Ovarian Cancer

Cviic, Diana; Jagarlamudi, Kiran; Meglic, Leon; Skof, Erik; Zore, Andrej; Lukanovic, David; Eriksson, Staffan; Osredkar, Josko


Simple Summary Ovarian cancer is one of the most difficult tumors to detect and manage. Usually, it is diagnosed in late stage of the disease which is associated with poor prognosis. Therefore, it is important to detect this cancer in the early stages to improve overall survival. In this study, we determined TK1 protein and TK1 activity levels as well as the biomarkers CA 125, HE4, and the ROMA index. Elevated TK1 protein levels were found in both benign and ovarian tumor (borderline and malignant ovarian cancer) patients. The combination of TK1 protein with CA 125 or HE4 showed higher sensitivity compared to the ROMA index. Therefore, the TK1 protein is a promising serum biomarker that can complement CA 125 or HE4 in the diagnostics of the early stages of ovarian cancer. Background: The early detection of ovarian cancer is presently not effective, and it is crucial to establish biomarkers for the early diagnosis of ovarian cancer to improve the survival of patients. Materials and methods: The aim of this study was to investigate the role of thymidine kinase 1 (TK1) in combination with CA 125 or HE4 to serve as a potential diagnostic biomarkers for ovarian cancer. In this study, a set of 198 serum samples consisting of 134 ovarian tumor patients and 64 healthy age-matched controls were analyzed. The TK1 protein levels in serum samples were determined using the AroCell TK 210 ELISA. Results: A combination of TK1 protein with CA 125 or HE4 showed better performance than either of them alone in the differentiation of early stage ovarian cancer from the healthy control group, but also a significantly better performance than the ROMA index. However, this was not observed using a TK1 activity test in combination with the other markers. Furthermore, the combination of TK1 protein and CA 125 or HE4 could differentiate early stage disease (stage I, II) more efficiently from advanced-stage (stage III, IV) disease (p < 0.0001). Conclusions: The combination of TK1 protein with CA 125 or HE4 increased the potential of detecting ovarian cancer at early stages.


thymidine kinase 1; TK 210 ELISA; TK-Liaison; CA 125; HE4; ROMA index; ovarian cancer

Published in

2023, Volume: 15, number: 5, article number: 1593
Publisher: MDPI

    Sustainable Development Goals

    Ensure healthy lives and promote well-being for all at all ages

    UKÄ Subject classification

    Clinical Laboratory Medicine
    Cancer and Oncology

    Publication identifier


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