A103-02 Circulating NETs as Biomarker for Sepsis Severity in Solid Tumor Patients

Background Sepsis in cancer patients poses a significant clinical and healthcare burden with cancer patients accounting for 10-20% of all sepsis cases, and in-hospital mortality rates ranging from 25-55%. Solid tumor patients with sepsis experience 2-5 times higher mortality compared to non-cancer patients. Timely diagnosis is critical, yet existing clinical tools often detect sepsis too late for optimal intervention. Neutrophil extracellular traps (NETs) have emerged as key players in promoting inflammation, endothelial dysfunction, and immune dysregulation—major drivers of sepsis pathophysiology. However, their utility as biomarkers in cancer-associated sepsis has not been systematically studied. Methods Here we conducted a prospective observational study to quantify cell-free nucleosomes as component of circulating NETs in solid tumor patients diagnosed with sepsis and septic shock; and assess their association with immune response, sepsis severity and clinical outcomes. Nucleosomes were measured using a validated assay targeting NET associated histone DNA complex. Circulating immune markers were quantified by Procartaplex assay. Association with clinical parameters including lactate levels, severity (SOFA) and 30-day mortality were analyzed. Results A total of 96 solid cancer patients were analyzed. Thirty patients were diagnosed with sepsis, 21 with septic shock and 47 served as control without sepsis or septic shock. Nucleosome levels at the time of enrollment were significantly elevated in patients with sepsis or septic shock compared to those without sepsis (p < 0.001), and showed strong correlation with SOFA scores similar to lactate (p = 0.003). Longitudinal analysis over 7 days also showed a significant positive correlation. Septic shock patients exhibited nucleosome levels in these patients correlated with neutrophil maturation suggesting that immature neutrophils are likely the main source of circulating NET associated nucleosomes. Conclusions Circulating NET associated nucleosomes are elevated in solid tumor patients with sepsis and are associated with worse clinical outcomes. Combined measurement of NET nucleosomes with other sepsis biomarkers such as lactate may enhance early risk stratification and guide therapeutic decision-making in this high-risk group.