Bioinformatics Analysis of the Cross-talk Between Idiopathic Pulmonary Fibrosis and Hashimoto's Thyroiditis on the Hub Genes and Key Pathways

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a disease of unknown cause, and there is increasing evidence that Hashimoto's thyroiditis (HT) is closely related to IPF. However, the mechanism of their interaction relationship remains unclear. The purpose of this study was to explore the common genetic features and underlying molecular and immune mechanisms between HT and IPF. Methods: Microarray data of HT and IPF were obtained from the Gene Expression Omnibus (GEO) database. The R software was used to identify the differential genes between two datasets and take the common differential genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of common DEGs present in HT and IPF using R software. The protein-protein interaction (PPI) network of their DEGs was constructed Utilizing the Search Tool for Retrieval of Interacting Genes/Proteins (STRING) database, identified and visualized hub genes by the Cytoscape software. To further investigate the diagnostic value of the hub genes, the receptor operating characteristic (ROC) curves were constructed utilizing the ‘pROC’ package. Subsequently, ROC analysis in two independent GEO datasets further validates the diagnostic value of these six hub genes. A miRNA-gene interactions network, TF-gene interactions network, and TF-miRNA coregulatory network were constructed by the NetworkAnalyst using hub genes and visualized by the Cytoscape for further analysis. In addition, R software was also applied to analyze immunological infiltration. Results: A total of 572 common DEGs were identified from the two datasets for subsequent analysis, which were primarily enriched in immune and inflammatory-related pathways. The plug-in ‘cytoHubba’ of the Cytoscape software was utilized to recognize six shared hub genes after validation, including CYBB, CD68, CD8A, CCL2, CCL5, and PTPRC. We predicted the miRNAs related to hub genes, including miR-106b-5p, miR-155-5p, miR-98-5p, let-7g-3p, and potential TFs (SPI1, NFKB1, NFKB2) through the interaction network. In addition, immune cell infiltration analysis revealed a significant infiltration of central memory CD4+ T cells infiltration in both IPF and HT samples. Conclusions: Bioinformatics studies reveal the common pathogenesis and immunological features between Hashimoto's thyroiditis and idiopathic pulmonary fibrosis. These common pathways and hub genes may serve as molecular biomarkers for diagnosable as well as prognostic assessment, providing new targets and ideas for further mechanistic studies. Additionally, the immune system plays a crucial role in the initiation and progression of both diseases. Keywords: idiopathic pulmonary fibrosis, Hashimoto's Thyroiditis, hub gene, immune process, bioinformatics