Proteomic analysis of premature umbilical cord blood and its relationship with bronchopulmonary dysplasia

Abstract

Abstract Background Bronchopulmonary dysplasia (BPD) frequently occurs in preterm infants, causing significantly impaired lung function and increased mortality rates. Studies on plasma protein levels can facilitate early detection of BPD, enabling prompt intervention and a decrease in mortality. Methods We conducted a prospective observational study involving proteomic sequencing of plasma samples from 19 preterm infants. Our analysis included principal component analysis, volcano plots, heatmap analysis, enrichment analysis, and receiver operating characteristic (ROC) analysis. Results Infants with BPD were characterized by increased levels of lipopolysaccharide (LPS)-binding protein (LBP), X-ray repair cross-complementing protein 6 (XRCC6), GLI pathogenesis-related 1 (GLIPR1), Golgi membrane Protein 1(GOLM1), immunoglobulin kappa variable (IGKV1-5), and immunoglobulin kappa variable 1–33 (IGKV1-33) in cord blood. Additionally, gene pathway analysis revealed a significant correlation between the pathways associated with these genes and BPD, particularly pathways involved in the immune system, innate immune system, neutrophil degranulation, prion diseases, regulation of the actin cytoskeleton, and the MAPK signaling. The proteins amine oxidase copper containing 3 (AOC3) and H4 clustered histone 6 (H4C6) were diagnostically significant. Additionally, H4C6 was negatively correlated with intraventricular haemorrhage and patent ductus arteriosus, and positively correlated with antenatal steroid administration. AOC3 was also positively correlated with antenatal steroid use. Conclusions Our findings suggest that the development of BPD is associated with changes in the plasma proteome of preterm infants. Specifically, the levels of AOC3 and H4C6 in the bloodstream could serve as biomarkers for the early detection of BPD in preterm infants. Furthermore, we found that GOLM1, lipopolysaccharide (LPS)-binding protein, XRCC6, and the contribution of neutrophil degranulation may play a crucial role in the development of therapies for BPD.

Keywords

• Bronchopulmonary dysplasia
• Plasma proteomics
• Preterm infants
• Biomarkers