Identification of 3 key genes as novel diagnostic and therapeutic targets for OA and COVID-19

Frontiers in Immunology

Immunology

Tianyang Xu¹  Zhengwei Duan¹  Yuesong Fu¹  Yiwei Zhang¹  Yonghao Guan¹  Guodong Li¹ 

[1]Department of Orthopedics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China

关键词: osteoarthritis;    SARS-CoV-2 infection;    COVID-19;    single-cell analysis;    drug prediction;   

DOI  :  10.3389/fimmu.2023.1167639

 received in 2023-02-16, accepted in 2023-05-10,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundCorona Virus Disease 2019 (COVID-19) and Osteoarthritis (OA) are diseases that seriously affect the physical and mental health and life quality of patients, particularly elderly patients. However, the association between COVID-19 and osteoarthritis at the genetic level has not been investigated. This study is intended to analyze the pathogenesis shared by OA and COVID-19 and to identify drugs that could be used to treat SARS-CoV-2-infected OA patients.MethodsThe four datasets of OA and COVID-19 (GSE114007, GSE55235, GSE147507, and GSE17111) used for the analysis in this paper were obtained from the GEO database. Common genes of OA and COVID-19 were identified through Weighted Gene Co-Expression Network Analysis (WGCNA) and differential gene expression analysis. The least absolute shrinkage and selection operator (LASSO) algorithm was used to screen key genes, which were analyzed for expression patterns by single-cell analysis. Finally, drug prediction and molecular docking were carried out using the Drug Signatures Database (DSigDB) and AutoDockToolsResultsFirstly, WGCNA identified a total of 26 genes common between OA and COVID-19, and functional analysis of the common genes revealed the common pathological processes and molecular changes between OA and COVID-19 are mainly related to immune dysfunction. In addition, we screened 3 key genes, DDIT3, MAFF, and PNRC1, and uncovered that key genes are possibly involved in the pathogenesis of OA and COVID-19 through high expression in neutrophils. Finally, we established a regulatory network of common genes between OA and COVID-19, and the free energy of binding estimation was used to identify suitable medicines for the treatment of OA patients infected with SARS-CoV-2.ConclusionIn the present study, we succeeded in identifying 3 key genes, DDIT3, MAFF, and PNRC1, which are possibly involved in the development of both OA and COVID-19 and have high diagnostic value for OA and COVID-19. In addition, niclosamide, ciclopirox, and ticlopidine were found to be potentially useful for the treatment of OA patients infected with SARS-CoV-2.

【 授权许可】

Unknown   
Copyright © 2023 Zhang, Duan, Guan, Xu, Fu and Li

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