Identification of key genes associated with Idiopathic Pulmonary Fibrosis by combining multiple analytical methods

Abstract Idiopathic Pulmonary Fibrosis (IPF) is the most common type of idiopathic interstitial pneumonias (IIPs) with unclear etiology and lack of effective diagnostic biomarker or therapeutic targets. This study aimed to identify the key genes associated with IPF through multiple microarray datasets. two datasets including GSE32537 and GSE110147 retrieved from Gene Expression Omnibus (GEO) database were used as training dataset (N =169) and external validation dataset (N =33). A total of 365 differentially expressed genes (DEGs) were identified between normal tissue and IPF tissue in the training dataset. Function enrichment analysis result indicated that these genes were involved in cell proliferation, response to stimulus, cellular process and immune system process. We then constructed a protein-protein network (PPI) using the cytoscape software based on the DEGs and the hub modules were screened using the MCODE algorithm. Then the DEGs from hub modules were further exploited into Least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM) analysis in the training dataset. 13 key genes including SERPIND1, CDH2, CP, WDR63, DNAH5, FGG, THBS1, VCAM1, COL1A2, POSTN, CXCL12, MMP13, SERPINE1 were further validated in the validation dataset. In addition, we also applied the CIBERSORT algorithm to evaluate the infiltration level of immune cells in IPF tissue, and the correlation between key genes and infiltrating immune cells. We identified that Plasma cells, CD4 naive T cells, NK resting cells, Monocytes, Mast resting cells and Neutrophils might involved in the process of IPF. Moreover, we also identified several drugs including pregnenolone, indoprofen, ramipril, inburnine may contribute to the treatment of IPF. In conclusion, the 13 genes might serve as potential diagnostic markers of IPF, and the immune cell infiltration plays an essential role in the occurrence and progression of IPF.