ArticleCancers2026
The Role of Circulating Extracellular DNA in Patients with Bladder Cancer: Clinical Associations and Exploratory Links with Heart Rate Variability.
Article in Cancers, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundExtracellular DNA (extracellular DNA) is a promising biomarker for tumor burden and systemic inflammation. However, its clinical significance in urothelial carcinoma remains unclear. This study evaluated plasma extracellular DNA (nuclear and mitochondrial fractions) and DNase activity in patients with bladder cancer (BC) in comparison to healthy controls, and explored their associations with tumor stage, survival, and heart rate variability (HRV) as a non-invasive marker of autonomic regulation.
methodsWe prospectively analyzed 84 subjects: 63 patients with urothelial carcinoma (52 non-muscle-invasive [NMIBC]; 11 muscle-invasive [MIBC]) and 21 healthy controls. Plasma extracellular DNA was quantified fluorometrically, while ncDNA and mtDNA fractions were assessed via quantitative real-time PCR. DNase activity was determined using the single radial enzyme diffusion assay. Clinical associations were evaluated through group comparisons, multivariable logistic regression, survival analysis, and correlation with HRV parameters.
resultsPatients with BC exhibited slightly but significantly higher extracellular DNA compared to healthy controls (by 9%); ncDNA showed a similar trend. Regarding disease progression, ncDNA demonstrated a stronger association with tumor stage than total extracellular DNA, with the highest concentrations observed in patients with MIBC. In multivariable logistic regression models adjusted for age, BMI, sex, smoking, and alcohol consumption, extracellular DNA remained independently associated with BC status (OR 5.99, 95% CI 1.43-25.12,
conclusionsCirculating extracellular DNA and ncDNA are independently associated with BC, with ncDNA showing a stronger correlation with tumor stage. While prognostic value regarding survival was not confirmed in this cohort, the absence of extracellular DNA-HRV correlations in patients, despite significant associations in healthy controls, suggests the loss of physiological coupling between circulating DNA and autonomic regulation. Further longitudinal studies are needed to validate the clinical utility and biological interpretation of these markers.
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