Genetic Programs Between Steroid-Sensitive and Steroid-Insensitive Interstitial Lung Disease

Abstract

The effectiveness of corticosteroids (GCs) varies greatly in interstitial lung diseases (ILDs). In this study, we aimed to compare the gene expression profiles of patients with cryptogenic organizing pneumonia (COP), idiopathic pulmonary fibrosis (IPF), and non-specific interstitial pneumonia (NSIP) and identify the molecules and pathways responsible for GCs sensitivity in ILDs. Three datasets (GSE21411, GSE47460, and GSE32537) were selected. Differentially expressed genes (DEGs) among COP, IPF, NSIP, and healthy control (CTRL) groups were identified. Functional enrichment analysis and protein–protein interaction network analysis were performed to examine the potential functions of DEGs. There were 128 DEGs when COP versus CTRL, 257 DEGs when IPF versus CTRL, 205 DEGs when NSIP versus CTRL, and 270 DEGs when COP versus IPF. The DEGs in different ILDs groups were mainly enriched in the inflammatory response. Further pathway analysis showed that “interleukin (IL)-17 signaling pathway” (hsa04657) and “tumor necrosis factor (TNF) signaling pathway” were associated with different types of ILDs. A total of 10 genes associated with inflammatory response were identified as hub genes and their expression levels in the IPF group were higher than those in the COP group. Finally, we identified two GCs’ response-related differently expressed genes (FOSL1 and DDIT4). Our bioinformatics analysis demonstrated that the inflammatory response played a pathogenic role in the progression of ILDs. We also illustrated that the inflammatory reaction was more severe in the IPF group compared to the COP group and identified two GCs’ response-related differently expressed genes (FOSL1 and DDIT4) in ILDs.