Circulating NETosis biomarkers in oncology

The use of minimally invasive circulating biomarkers is becoming increasingly important in cancer management, aiding in diagnosis, risk stratification, therapeutic monitoring, and evaluation of clinically relevant complications. Neutrophil activation and extracellular trap formation are increasingly recognized biological processes in cancer-related inflammation, thrombosis, and host-tumor interactions. Circulating biomarkers of these processes, such as myeloperoxidase, neutrophil elastase, citrullinated histone H3, myeloperoxidase-DNA complexes, cell-free DNA, and nucleosome-associated markers, can be detected in blood-based samples and potentially offer clinically relevant data in oncology. This review assesses the diagnostic, prognostic, and monitoring capabilities of circulating biomarkers of neutrophil activation and NETosis in cancer, focusing on their implications for clinical chemistry and diagnostic laboratory medicine. We synthesized existing evidence showing that these analytes are associated with adverse clinicopathological features, poor survival, systemic inflammation, and cancer-related thrombosis. We also discuss their possible applications in risk stratification, complication evaluation, longitudinal disease tracking, and complementary interpretation of established tumor markers. This review identifies laboratory parameters that influence clinical implementation, such as specimen matrix selection, preanalytical variability, assay heterogeneity, analytical validation, and reporting standardization. We also addressed interpretive issues due to limited disease specificity and confounding inflammatory, infectious, and thrombotic diseases. However, current predictive and longitudinal-monitoring evidence remains exploratory because most studies are small, assay-heterogeneous, and lack externally validated clinical decision thresholds. Overall, translating neutrophil activation- and NETosis-associated biomarkers into routine diagnostic laboratory practice will involve harmonized assays, standardized workflows, prospective clinical validation, and demonstrable incremental value for the management of patients. This review presents a laboratory medicine-centered perspective for understanding the opportunities and existing constraints of these emerging adjunctive biomarkers in cancer research.