Pediatric patients with cancer exhibit increased neutrophil extracellular traps and reduced active deoxyribonuclease I: diagnostic, prognostic, and therapeutic opportunities

Background: Neutrophil extracellular traps (NETs) con tribute to cancer progression; however, their value as sys temic biomarkers and therapeutic targets in pediatric cancers remains unclear.Purpose: To evaluate circulating NET markers as mini mally invasive diagnostic and prognostic biomarkers in pediatric cancer and explore the restoration of NET de gradation as a therapeutic strategy using recombinant human deoxyribonuclease I (DNaseI).Methods: In this prospective cohort study, plasma sam ples from 182 pediatric patients with diverse tumor types and 10 agematched healthy controls were analyzed.Cir culating NET markers, including cellfree DNA, calpro tectin, neutrophil elastase, citrullinated histone H3-DNA complexes, and DNaseI activity, were quantified.NETs were assessed in tumor tissue samples using immuno fluorescence.The diagnostic performance and progno stic value were evaluated using receiver operating charac teristic and survival analyses, respectively.The ability of patient plasma to degrade NETs and the effects of recom binant human DNaseI supplementation were examined in vitro.Results: Plasma cellfree DNA and calprotectin levels were significantly higher in pediatric patients with cancer than in controls, particularly in highrisk patients.Cell free DNA showed high diagnostic accuracy, whereas calprotectin and DNaseI activity discriminated between high and lowrisk patients and were associated with ad verse outcomes.NETs were detected in tumor tissues with heterogeneous distribution and no consistent association with prognosis.Plasma from highrisk patients exhibited impaired NET degradation, which was restored in vitro using recombinant human DNaseI.Conclusion: Circulating NETs, especially cellfree DNA and calprotectin, show promise as noninvasive diagnostic and prognostic biomarkers for pediatric cancers.Reduced DNaseI activity identified a potentially targetable mecha nism, supporting further investigation of DNaseIbased therapeutic strategies for highrisk pediatric tumors.