Integrated bioinformatics analysis of key candidate genes and therapeutic drugs for idiopathic pulmonary fibrosis

• 作者: Cai-Zhen Yang Chang-Wen Zhang Guang-Nan Liu Jia-Yu Zhang Ming-Peng Xu Tong-Tong Zhang Wen-Tao Li Yin-Kang Li Yu Li
• 来源期刊: 亚洲毒理学研究
• 学科: 医学
• 关键词: Idiopathic pulmonary fibrosis Bioinformatics analysis Differentially expressed genes Molecular targeted therapy
• 年，卷（期）: 2020,（4）
• 页码范围: 151-164
• 页数: 14页
• 分类号: R73

摘要

Background: Idiopathic pulmonary fibrosis is a form of fibrotic and fatal lung disease worldwide with unknownetiology and mechanisms. This manuscript focused on clarifying the core protein-protein interaction network, genesand related pathways correlated with idiopathic pulmonary fibrosis in detail. Methods: Gene chip (GSE24206) wasacquired from the Gene Expression Omnibus database. GEO2R was a R-based online tool to screen differentialexpressed genes. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis were utilized toascertain gene function and key signaling pathways. The Search Tool for the Retrieval of Interacting Genes was usedto construct the protein-protein interaction network. Key genes and module analysis were screened out usingCytohubba and MCODE plugin. The candidate therapeutic molecular drugs were searched for IPF using DGIdbdatabase. Results: A cohort of 240 differential expression of genes (113 up-regulated and 127 down-regulated) wereknocked out. Gene Ontology enrichment analysis indicated that some differential expression of genes were involvedin extracellular matrix and neutrophil chemotaxis. The Kyoto Encyclopedia of Genes and Genomes pathways werepredominantly involved in chemokine signaling pathway and ECM-receptor interactions. Two significant modulesand 5 hub genes were strongly implicated in idiopathic pulmonary fibrosis from protein-protein interaction network.The 2 module genes were primarily enriched in the cytokine-cytokine receptor, TNF signaling pathway, toll-likesignaling pathway, and Wnt signaling pathway. Finally, 41 small molecules were identified by DGIdb database as thepotential drugs of idiopathic pulmonary fibrosis. Conclusion: To conclude, in this study, the hub genes, signalingpathways, and small molecules will conduce to better understanding the mechanisms and may provide new methodsto the therapy of idiopathic pulmonary fibrosis.