Meta-analysis links serum TK1 to prostate cancer and tumor grade

A systematic review and meta-analysis of eight studies found that serum thymidine kinase 1 (TK1), a DNA-synthesis enzyme used as a marker of cellular proliferation, was significantly elevated in people with prostate cancer compared with healthy controls and patients with no evidence of malignancy. The pooled analysis included 868 patients with prostate cancer, 320 patients with no evidence of malignancy, and 900 healthy controls. It also found that people whose prostate tumors had higher Gleason scores tended to have higher serum TK1 concentrations, linking the blood marker with tumor aggressiveness in the populations studied.

Researchers searched PubMed, Scopus, and Embase for studies reporting serum TK1 concentrations in people with prostate cancer. They used Review Manager to compare TK1 levels across three groups: prostate cancer, no evidence of malignancy, and healthy controls. Relative to healthy controls, people with prostate cancer had a standardized mean difference in TK1 of 1.51 (95% confidence interval, 1.06–1.95; p<0.00001).

The difference between prostate cancer and the no-evidence-of-malignancy group was smaller but remained statistically significant, at 0.55 (95% confidence interval, 0.12–0.98; p=0.01). These results show an association between elevated circulating TK1 and the presence of prostate cancer in the pooled study populations. The review also assessed whether TK1 tracked pathological tumor grade.

Patients with Gleason score 7 tumors had higher TK1 levels than those with Gleason scores of 6 or lower, with a standardized mean difference of −0.58 (95% confidence interval, −1.07 to −0.09; p=0.02), where the sign reflects the direction of the comparison with the lower-grade group. People with Gleason scores of 8 or higher also had higher TK1 levels than patients with scores of 6 or lower, producing a standardized mean difference of 0.69 (95% confidence interval, 0.04–1.35; p=0.04). Both grade comparisons were statistically significant, although the confidence interval for the Gleason 8-or-higher comparison was wide.

The analysis therefore supports an association between higher serum TK1 and more aggressive prostate tumors, rather than demonstrating that TK1 causes grade progression or independently predicts an individual outcome. Diagnostic performance was less uniform. Across studies, areas under the receiver operating characteristic curve ranged from 0.67 to 0.97, and the TK1 concentration thresholds used for diagnosis varied widely.

The review reported that standardized mean differences, areas under the curve, and correlation coefficients for TK1 in the study groups compared with controls were relatively higher than the corresponding measures for prostate-specific antigen (PSA). The comparison addresses assay performance in the included literature, but it does not establish that TK1 can replace PSA or that the two markers provide identical information. PSA was described in the study background as an early-screening biomarker whose specificity is limited because it can also be elevated in benign conditions, whereas TK1 was examined as a serum-based marker of cellular proliferation.

Taken together, the findings position serum TK1 as a possible complementary biomarker for prostate-cancer risk stratification and prognostication. The authors noted that TK1 can be tested by enzyme-linked immunosorbent assay (ELISA) and suggested that it might be useful in low-resource settings, but the evidence presented here remains pooled evidence from eight studies rather than proof of routine clinical benefit. The main limitations evident in the reported results are the limited number of included studies, wide variation in diagnostic cutoffs, and imprecision in at least one tumor-grade comparison.

Subject of Research: Serum thymidine kinase 1 as a marker of prostate cancer presence and tumor aggressiveness

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

Article References: Bhattarai, A., Paudel, S., Sah, S., Sah, R., & Shuck, S. C. (2026). Thymidine kinase 1 is elevated in prostate cancer and correlates with tumor aggressiveness: a systematic review and meta-analysis. BMC Cancer. https://doi.org/10.1186/s12885-026-16908-0

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16908-0

Keywords: prostate cancer, thymidine kinase 1, serum biomarker, tumor aggressiveness, Gleason score, meta-analysis, systematic review, PSA, cancer diagnosis, cell proliferation, Thymidine, kinase