Elevated DUOX2 levels correlate with necrotizing enterocolitis development.

Background: Neonatal necrotizing enterocolitis (NEC) is a life-threatening intestinal disease primarily affecting preterm infants. Although the exact pathophysiology remains unclear, immune responses and redox reactions play crucial roles in its development. Methods: We identified Dual Oxidase 2 (DUOX2) as a significantly upregulated gene in the intestinal tissues of NEC patients. Subsequent analyses included Gene Ontology (GO) enrichment and immune infiltration profiling related to DUOX2. Using a nested case-control design, we then evaluated the clinical relevance of serum DUOX2 protein levels in preterm infants with NEC (gestational age <32 weeks). Results: DUOX2 was significantly highly expressed in NEC intestinal tissues, with an AUC value of 0.844 (0.599-1.000) predicting the occurrence of NEC. GO enrichment analysis revealed that the differentially expressed genes (DEGs) between the NEC and control groups mainly affect redox reactions, including reactive oxygen species (ROS) and superoxide. Immunoinfiltration analysis revealed a positive correlation between DUOX2 expression and plasma cells (R=0.69, P=0.041). Univariate and multivariate analyses identified high levels of serum DUOX2 as a risk factor for developing NEC. Serum DUOX2 levels were negatively correlated with albumin levels and positively correlated with red blood cell distribution width and lactate dehydrogenase levels. The AUC value of serum DUOX2 levels for diagnosing NEC was 0.809 (95% CI: 0.712-0.906), with an optimal cut-off value of 2.483 ng/mL, a sensitivity of 91.30%, and a specificity of 78.26%. Conclusion: This study demonstrates a significant association between elevated DUOX2 expression and the development of NEC in preterm infants.