Signal Pathway Analysis Of Differentially Expressed Genes And Identification Of Key Genes In Idiopathic Pulmonary Fibrosis

BackgroundIdiopathic pulmonary fibrosis is an unknown and irreversible chronic progressive diffuse pulmonary parenchyma disease involving alveoli and pulmonary interstitium,characterized by progressive decline of pulmonary function and continuous aggravation of dyspnea.The pathogenesis of IPF is unknown,but the incidence is on the rise.At present,there is no effective treatment.Exploring the biological pathways involved in the development of IPF or finding biomarkers to guide the diagnosis and treatment of the disease is an important topic in the research of pulmonary fibrosis.In recent years,due to the vigorous development of microarray chip technology and next generation sequencing technology,especially the wide application of gene chip,it has brought convenience for human beings to understand the occurrence and development mechanism of diseases at the genetic level,and derived a large number of high-throughput databases,such as Gene Expression Omnibus database,which is by far the largest unified management public gene expression database in the world.Based on the data in GEO,it is a new scientific research method to analyze the changes of diseases at the genetic level,and then analyze the important signal pathways and key genes involved in the diseases.ObjectiveThe purpose of this study is to use R language to analyze the changes of genes expression in IPF in GEO database,to analyze the signal pathways and to identify the key genes in the IPF patients,so as to analyze the clinical application value of Hub gene in IPF.MethodWe downloaded the expression profile of GSE110147 and GSE53845 datasets from the GEO database.Both the GSE110147 and GSE53845 datasets contain the information of gene expression in lung tissues of patients with IPF and healthy people.Taking the GES110147 dataset as the training set,the gene expression data of GSE110147 were analyzed by R software to determine the differentially expressed gene between IPF patients and controls.The protein-protein interaction network and significantly differentially expressed genes was analyzed by STRING database and Cytoscape software.And then the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were carried out by Cluster file R package.Then,the hub genes were screened out with the help of GSE53845 verification set and their expression level among IPF patients of different genders were analyzed.Finally,we summarized the potential diagnostic and prognostic value of five Hub genes in IPF according to the published literature.ResultFinally,in the training set,376 DEGs were obtained,of which 234 genes were up-regulated and 142 genes were down-regulated.GO and KEGG analysis showed these genes were mainly involved in the cell cycle and its regulatory process and herpes simplex virus infection.In addition,five key genes,CCL2,COL1A1,SPP1,MMP1 and MMP7 were screened through the verification dataset.Among them,MMP1,SPP1 and MMP7 were over-expressed in female IPF patients,but there was no statistical difference.Combined with the existing research reports,we found these Hub genes had important clinical significance for the diagnosis and prognosis of IPF.ConclusionWe identified five hub genes and possible biological pathways that were closely related to the occurrence of IPF,and confirmed the expression of COL1A1,SPP1,MMP1 and MMP7 genes were increased in IPF.These genes especially SPP1,MMP1 and MMP7 have potential roles in diagnosing and predicting the prognosis of IPF,which provides a basic insight for further study of the pathogenesis,diagnosis and treatment of IPF.