The Role of APOL1 in Necrotizing Enterocolitis and Its Promise as a Diagnostic Biomarker.

OBJECTIVE: Necrotizing enterocolitis (NEC) is a severe inflammatory disease of the intestine. Although previous studies have demonstrated that APOL1 plays an important role in regulating macrophage polarization and immune-mediated inflammatory diseases, its specific function in NEC remains unclear. We aim to further explore the role of APOL1 in NEC and its efficacy as a diagnostic biomarker. METHODS: We performed tissue transcriptomic and plasma proteomic analyses based on clinical samples from preterm infants with NEC patients and conducted multilevel experimental validations. An in vitro macrophage polarization model was established to further investigate the regulatory role of APOL1 in macrophage differentiation. The diagnostic potential of APOL1 for NEC was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Multiomics analyses revealed a significant upregulation of APOL1 expression in NEC, which was further confirmed by qPCR, immunofluorescence, and ELISA. Pathway enrichment and immune infiltration analyses indicated that APOL1 is positively associated with M1 macrophage infiltration and the expression of multiple proinflammatory cytokines. Immunofluorescence staining further demonstrated that APOL1 is highly expressed in M1 macrophage-enriched regions. In vitro experiments showed elevated APOL1 expression in M1 macrophages, while its inhibition significantly reduced intracellular reactive oxygen species (ROS) accumulation and NF-κB p65 activation, thereby suppressing M1 polarization. Moreover, the combination of plasma APOL1 and lymphocyte count (LYM) demonstrated high diagnostic efficacy for NEC, with an AUC value of 0.96 (sensitivity 93.3% and specificity 93.3%). CONCLUSIONS: Our findings reveal a marked upregulation of APOL1 in preterm infants with NEC. Mechanistically, we propose that the APOL1-ROS-NF-κB axis constitutes a novel and promising therapeutic target for NEC intervention. Furthermore, the combined detection of plasma APOL1 and LYM demonstrates high efficacy.