Thymidine kinase as a biomarker of chemoresistance in epithelial ovarian cancer using the KELIM model

Lukanović, David (author), Osredkar, Joško (author), Škof, Erik (author), Cviič, Diana (author), Jerin, Aleš (author), Lešnik, Kaja (author), Matjašič, Miha (author), Meglič, Leon (author)

Background: Ovarian cancer (OC) remains the most lethal gynecological malignancy, with platinum sensitivity being a key determinant of treatment outcomes. The KELIM model, derived from CA-125 kinetics, is a promising biomarker for predicting chemosensitivity. Thymidine kinase 1 (TK1), a proliferation marker, has shown relevance in various cancers but its role in chemotherapy response for OC is unclear. Methods: In this retrospective study, we assessed the association between TK1 protein (TK1p) and enzymatic activity (TK1a) and chemosensitivity (KELIM), platinum-free interval (PFI), and chemotherapy response score (CRS) in 28 patients with epithelial OC treated with platinum-based chemotherapy. Biomarker dynamics were measured at multiple timepoints. KELIM was calculated using CA-125 kinetics; relationships with CRS and PFI were evaluated. Results: KELIM demonstrated robust predictive performance (correlating with favorable CRS [rho = 0.731, p = 0.011] and longer PFI [rho = 0.437, p = 0.007]). TK1p and TK1a showed no significant correlations with KELIM, PFI, or CRS. ROC analysis for preoperative TK1p yielded an AUC of 0.6941, indicating moderate discriminative potential. TK1a increased postoperatively but lacked predictive value for chemoresistance. Conclusion: Our findings reinforce the value of KELIM as a reliable predictor of platinum sensitivity in OC. TK1 dynamics reflect tumor proliferation but did not significantly predict chemotherapy response. Larger cohorts and further research are required to explore whether TK1 can complement established biomarkers.

• Language: English
• Keywords: biomarker, CA-125, chemoresistance, epithelial ovarian cancer, KELIM, ovarian cancer, thymidine kinase
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2026
• Number of pages: 11 str.
• Numbering: Vol. 17, art. 1617484
• PID: 20.500.12556/RUL-182304
• UDC: 616-006:618.11
• ISSN on article: 1663-9812
• DOI: 10.3389/fphar.2026.1617484
• COBISS.SI-ID: 276854531
• Publication date in RUL: 08.05.2026

Record is a part of a journal

• Title: Frontiers in pharmacology
• Shortened title: Front. Pharmacol.
• Publisher: Frontiers Media
• ISSN: 1663-9812
• COBISS.SI-ID: 29551833

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: biomarkerji, CA-125, kemorezistentnost, epitelijski rak jajčnikov, KELIM, rak jajčnikov, timidin kinaza

Projects

• Funder: University Clinical Centre Ljubljana
• Project number: 20190069