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Improving Diagnostic Precision: Urine Proteomics Identifies Promising Biomarkers for Necrotizing Enterocolitis

Mackay, S.; Frazer, L. C.; Bailey, G. K.; Miller, C. M.; Gong, Q.; DeWitt, O. N.; Good, M.

2024-03-24 pediatrics
10.1101/2024.03.21.24304374 medRxiv
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BackgroundNecrotizing 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 methodsThe 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). ResultsNinety-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). ConclusionsUrine proteins significantly differ between infants with and without NEC, which supports their potential as future biomarkers. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/24304374v1_ufig1.gif" ALT="Figure 1"> View larger version (85K): org.highwire.dtl.DTLVardef@415ea9org.highwire.dtl.DTLVardef@1add162org.highwire.dtl.DTLVardef@8d8c41org.highwire.dtl.DTLVardef@f31b62_HPS_FORMAT_FIGEXP M_FIG Graphical abstract. Overview of study findings. Created with Biorender.com C_FIG

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