Unlike LBP, its structural relatives BPI, CETP and PLTP show no expression difference in necrotizing enterocolitis, isolating LBP as the disease-associated biomarker (J Pediatr Surg 2026)

Objectives: Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disease of neonates. This study aimed to identify Lipopolysaccharide-binding protein (LBP) as a potential biomarker for the diagnosis of NEC through multi-omics analyses and validation.

Methods: We analyzed LBP expression differences in NEC using transcriptomic data from our cohort (intestinal tissue samples from NEC cases and controls) integrated with a public gene expression dataset (GSE46619). Correlations between LBP and common clinical biomarkers (C-reactive protein (CRP), platelet count (PLT), white blood cell count (WBC), lymphocyte count) were evaluated using Spearman's correlation. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic performance of LBP alone and in combination with other biomarkers. Gene Ontology (GO) enrichment analysis was conducted to explore biological processes associated with LBP.

Results: LBP protein was significantly upregulated in NEC compared to controls, increasing with greater disease severity (stage III > stage II > stage I),and LBP expression showed strong positive correlations with inflammatory cytokines IL-6 and IL17RA in the transcriptomic analysis (P < 0.001). In contrast, other LBP-related proteins (BPI, CETP, PLTP) showed no significant difference between NEC and controls. LBP levels correlated positively with CRP (R = 0.7702, P < 0.0001) and negatively with lymphocyte count (R = -0.7269, P < 0.0001), while correlations with WBC and PLT were weak. In ROC analysis, LBP yielded an area under the curve (AUC) of 0.8252 for diagnosing NEC, with 64.1% sensitivity and 90.91% specificity, outperforming WBC, PLT, and other routine markers. Combining LBP with CRP improved the diagnostic AUC to 0.8834. Moreover, LBP levels and diagnostic accuracy were highest in advanced NEC stages (AUC for stage III 0.9702). GO enrichment suggested that LBP is involved in regulation of cellular responses to biological stimuli and immune cell movement, reflecting its role in the innate immune response.

Conclusion: LBP is significantly elevated in both the intestinal tissue and plasma of NEC patients and demonstrates high diagnostic sensitivity for the disease. Moreover, LBP shows strong diagnostic performance in assessing both NEC onset and disease progression, and its combination with routine hematological parameters may further enhance early identification and improve clinical management of NEC.