Background: Necrotizing enterocolitis (NEC) is a severe intestinal disease that primarily impacts preterm infants. Current diagnostic tools are inadequate, so urine proteomics was performed for patients with and without NEC to identify putative biomarkers. Research design and methods: The abundance of urinary proteins detected using an aptamer-based microarray was compared for infants with NEC (n=20) and controls, age-matched (n=8) or self-matched (n=12). Spearman r correlation and hierarchical cluster analysis were performed. The area under the curve (AUC) was calculated for receiver operator characteristic curves (ROC). Results: Ninety-nine proteins differed in NEC vs. controls based on median fold change (Log2 +/- 1.1) and significance (P < 0.05). Patterns of abundance were consistent for both types of matching, and samples clustered based on NEC severity. Two panels were built to differentiate between infants with and without NEC. Panel 1 included proteins associated with inflammation/NEC and produced by the intestinal epithelium (REG1B, REG3A, FABP2, DEFA5, AUC 0.90). Panel 2 consisted of proteins with the largest fold change between NEC vs. controls and the highest individual AUC values (REG1B, SSBP1, CRYZL1, ITM2B, IL36B, IL36RN, AUC 0.98). Conclusions: Urine proteins significantly differ between infants with and without NEC, which supports their potential as future biomarkers.

The authors have declared no competing interest.

This study was funded by the following: LCF is supported by a Thrasher Research Fund Early Career Award, UNC School of Medicine Physician Scientist Training Program Faculty Award, and UNC Childrens Development Early Career Investigator Grant through the generous support of donors to UNC. MG is supported by National Institutes of Health (NIH) grants R01DK124614, R01DK118568, R01HD105301, R44HD110306, the Chan Zuckerberg Initiative Grant number 2022-316749, and the University of North Carolina at Chapel Hill Department of Pediatrics.

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