Early Identification of Bronchopulmonary Dysplasia Using Novel Biomarkers by Proteomic Screening

Confirmation of protein expression in ELISA technique (SIGLEC-14 [sialic acid-binding Ig-like lectin 14], R&D Systems; BCAM [basal cell adhesion molecule], Thermo Fisher Scientific; ANGPTL3 [angiopoietin-like 3 protein], Raybiotech) used one to two samples from the first week of life. Paraformaldehyde tissue sections from autopsy lungs of five infants with BPD and an infant with a nonpulmonary cause of death (Sophia Children's Hospital, Erasmus Medical Center, Rotterdam; gestational age, 26.6 6 2.0 wk; mechanical ventilation, 42 6 14 d, each mean 6 SD) demonstrated pulmonary protein expression (SIGLEC-14, 1:50, #MAB10721, R&D Systems; BCAM, 1:200, #sc-99188, Santa Cruz Biotech; ANGPTL3, 1:50,#600401-Y15, Rockland; secondary antibody 1:300; Vector ABC reagent, 3,3'-diaminobenzidine). [...]to identify diseaserelated biomarkers, we fitted a generalized additive model including disease information (BPD 0 vs. Results After correction for clinical confounding variables (Table 1), 12 proteins were significantly regulated in preterm infants developing BPD (Figure 1A; P < 0.1; false discovery rate, 0.053-0.096), reflecting the Gene Ontology categories identified by functional enrichment analysis (e.g., immune function, defense response, extracellular matrix, cellular proliferation, cellular migration, and organ development).