Weighted gene coexpression network reveals downregulation of genes in bronchopulmonary dysplasia

Pediatr Pulmonol. 2021 Feb;56(2):392-399. doi: 10.1002/ppul.25141. Epub 2020 Nov 24.

Abstract

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 coexpression network using weighted gene coexpression network analysis. The analysis was carried out on the GSE8586 dataset, 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 coexpression module related to the BPD phenotype. It was significantly enriched in genes related to human T-cell leukemia virus infection and the mitogen-activated protein kinase pathway. In this module, the expression of the following four hub genes in infants with BPD was significantly decreased: Fos proto-oncogene (FOS), BTG antiproliferation 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.

Keywords: bronchopulmonary dysplasia; prediction biomarkers; preterm infants; weighted gene coexpression network analysis.