Blood enzyme marker shows promise for lung cancer risk assessment in pooled analysis

Serum thymidine kinase 1 protein, a marker of cell proliferation, rises steadily across the spectrum of lung health, according to a systematic review and meta-analysis published in Discover Oncology. The pooled analysis found that levels climb from tumor-free individuals through patients with pneumonia and benign or precancerous lung tumors to those with lung cancer, and that statistical models combining the protein with other predictors reached an area under the curve of 0.85 for assessing lung cancer risk.

The research team, led by Xuemei Huang, Xiaoyang Huang, Haidong Wang, Hongbo Ma and Jiang Xia, systematically searched PubMed, Web of Science and the China National Knowledge Infrastructure for observational studies that reported mean serum thymidine kinase 1 protein values with corresponding standard errors, or areas under the curve with 95 percent confidence intervals. After screening, 32 studies met the eligibility criteria and entered the meta-analyses, which pooled mean protein values, mean differences between groups, and model performance for predicting lung cancer risk.

The new analysis does not claim the protein alone can diagnose cancer, but it quantifies how strongly blood levels differ between people with and without malignant or premalignant lung disease across many independent studies.

The pooled results showed a clear gradient. Tumor-free individuals had the lowest serum thymidine kinase 1 protein levels, followed by pneumonia patients, then patients with benign and precancerous lung tumors, with lung cancer patients showing the highest values. One of the most precise comparisons involved tumor-free versus pneumonia groups: the pooled mean difference was -0.30, with a 95 percent confidence interval of -0.39 to -0.21, a p value below 0.001, moderate heterogeneity indicated by an I-squared of 32.91 percent, and 190 participants contributing to that estimate.

All three non-cancer groups shared a common direction of difference. The tumor-free, pneumonia, and benign and precancerous tumor groups each had significantly lower serum thymidine kinase 1 protein levels than the lung cancer group in the pooled analyses.

The performance figures came from multivariate models that incorporated the protein alongside other predictors. Across these models, the pooled area under the curve was 0.85, with a 95 percent confidence interval of 0.79 to 0.90, a p value below 0.001, an I-squared of 74.57 percent, and a total of 7,020 participants.

The authors concluded that multivariate models incorporating serum thymidine kinase 1 protein and other predictors might be used for the risk assessment of lung cancer. They emphasized a practical framing: an increase in model-predicted risk might advise doctors and patients to take further tests to diagnose potential lesions in the lung. The conclusion stops short of recommending the marker for routine screening, noting explicitly that further prospective research is required before such use can be justified.

Several limitations shape how these findings should be read. The underlying studies were observational, so the pooled estimates describe associations between protein levels and disease status rather than proving any causal or predictive relationship in individual patients. The meta-analysis aggregated mean values rather than individual patient data, which limits the ability to adjust for confounding or to evaluate performance in specific subgroups. Heterogeneity across studies, particularly for the pooled area under the curve, means the summary figures should be treated as approximate rather than definitive benchmarks.

The work appears in Discover Oncology and is published open access, making the pooled estimates available to researchers who may now design the prospective studies the authors say are needed to determine whether serum thymidine kinase 1 protein can earn a place in clinical risk assessment workflows.

Subject of Research: Systematic review and meta-analysis of serum thymidine kinase 1 protein levels and model performance for lung cancer risk assessment

Article Title: Performance of serum thymidine kinase 1 protein in lung cancer risk assessment: a systematic review and meta-analysis

Article References: Huang, X., Huang, X., Wang, H., Ma, H., & Xia, J. (2026). Performance of serum thymidine kinase 1 protein in lung cancer risk assessment: a systematic review and meta-analysis. Discover Oncology. https://doi.org/10.1007/s12672-026-06042-5

Image Credits: AI Generated

DOI: 10.1007/s12672-026-06042-5

Keywords: serum thymidine kinase 1, lung cancer, risk assessment, meta-analysis, systematic review, biomarker, cell proliferation, pooled analysis, observational studies, diagnostic accuracy, Performance, serum