Weighted Gene Co-Expression Network Reveals Down-Regulation of Genes in Bronchopulmonary Dysplasia.

BACKGROUND Bronchopulmonary dysplasia (BPD) is a serious lung disease observed in premature infants, known to cause considerable morbidity and mortality. Its prognosis is influenced by a complex network of genetic interactions. In this study, we determined the potential key factors in the pathogenesis of this condition. METHODS We constructed scale-free gene co-expression network using weighted gene co-expression network analysis (WGCNA). The analysis was carried out on the GSE8586 data set, which contains the expression profiles of umbilical cord tissue homogenates from 20 neonates with BPD and 34 unaffected controls. RESULTS Our analysis identified one significantly downregulated co-expression module related to the BPD phenotype. It was significantly enriched in genes related to human T-cell leukemia virus (HTLV-I) infection and the MAPK pathway. In this module, the expression of the following four hub genes in infants with BPD was significantly decreased: Fos proto-oncogene (FOS), BTG anti-proliferation factor 2 (BTG2), Jun proto-oncogene (JUN), and early growth response protein 1 (EGR1). The downregulation of these hub genes was verified in clinical samples derived from blood and umbilical cord tissue. CONCLUSION The decreased expression of FOS, BTG2, JUN, and EGR1 is associated with BPD and, therefore, could be used as biomarkers to diagnose early BPD. This article is protected by copyright. All rights reserved.