NINJ1 as a novel biomarker of intestinal injury in necrotizing enterocolitis

Necrotizing enterocolitis (NEC) remains a lethal gastrointestinal emergency in neonates with an elusive etiology. Ninjurin-1 (NINJ1) mediates plasma membrane rupture during lytic cell death, yet its role in NEC remains undefined. This study investigated the clinical relevance of NINJ1 in NEC progression and evaluated its utility as a biomarker for disease severity. We conducted a prospective observational study quantifying serum NINJ1 levels via ELISA in 68 neonates with NEC and 42 gestational age-matched controls without infection. The NEC cohort was stratified by treatment modalities and complications into surgical vs. medical management, and perforated vs. non-perforated subgroups. Immunohistochemistry (IHC) of resected specimens and bioinformatics analysis of the public GSE46619 dataset were performed to evaluate tissue-level NINJ1 expression. Diagnostic performance for surgical intervention and perforation was assessed using receiver operating characteristic (ROC) analysis. Serum NINJ1 levels were significantly elevated in neonates with NEC compared to controls (p < 0.001). Stratified analysis revealed further significant increases in infants requiring surgery (n = 28) compared to those managed medically (n = 40) (p < 0.01), and in perforated (n = 26) versus non-perforated cases (n = 42) (p < 0.01). For predicting surgical intervention, NINJ1 (AUC: 0.73) outperformed PCT (AUC: 0.65) and CRP (AUC: 0.62). At a cutoff of 131.03 pg/mL, NINJ1 yielded a specificity of 85.1% for assessing surgical risk. Notably, a combined model integrating NINJ1, CRP, and PCT further improved the AUC for predicting surgical intervention to 0.79. Furthermore, NINJ1 demonstrated the strongest single predictive capacity for bowel perforation (AUC: 0.75). Circulating NINJ1 is significantly upregulated in severe NEC, particularly in cases complicated by perforation or requiring surgical intervention. These findings position NINJ1 as a promising biomarker for assessing the severity of intestinal injury in NEC neonates.