Thymidine kinase 1 is elevated in prostate cancer and correlates with tumor aggressiveness: a systematic review and meta-analysis

Abstract

Non-invasive biomarkers can inform prostate cancer diagnosis, surgical decision-making, and treatment. However, early screening biomarkers, including prostate-specific antigen (PSA), lack specificity due to elevation in benign conditions. Thymidine kinase 1 (TK1), a DNA synthesis enzyme, is a serum-based marker of cellular proliferation. We performed a meta-analysis to evaluate whether TK1 distinguishes prostate cancer from non-malignant states and reflects tumor aggressiveness. Literature searches in PubMed, Scopus, and Embase identified studies reporting serum TK1 concentrations in prostate cancer. Meta-analysis using RevMan compared TK1 levels across prostate cancer, no evidence of malignancy (NOMA), and healthy controls using standardized mean differences (SMDs). Associations with tumor aggressiveness were assessed by Gleason score (GS) ( ≤ 6, 7, ≥ 8) and by comparing SMDs, area under the curve (AUC), and correlations for TK1 versus PSA. Eight studies including 868 patients with prostate cancer, 320 with NOMA, and 900 healthy controls were analyzed. TK1 was significantly elevated in prostate cancer compared to both healthy controls [SMD: 1.51 95% CI: 1.06–1.95; p < 0.00001] and NOMA [SMD: 0.55 95% CI: 0.12–0.98; p = 0.01]. Patients with less aggressive prostate tumors (GS ≤ 6) had significantly lower TK1 than patients with more aggressive tumors (GS7 [SMD: -0.58 95% CI: -1.07 to -0.09; p = 0.02] and GS ≥ 8 [SMD: 0.69 95% CI: 0.04–1.35; p = 0.04]). Diagnostic cut-offs varied widely between studies, with AUCs ranging from 0.67 to 0.97. Overall, SMDs, AUCs, and correlation coefficients of TK1 in the study groups compared to controls were relatively higher than that of PSA. TK1 was significantly elevated in prostate cancer than healthy controls and NOMA. Prostate cancer patients with higher GS tumors showed high TK1 compared to patients with lower GS scores. In a low resource setting, TK1 testing, which can be performed by ELISA, might be a complementary biomarker in prostate cancer risk-stratification and prognostication.