Effect of DMARDs on differentially expressed genes in synovium of rheumatoid arthritis
10.3760/cma.j.cn141217-20220317-00090
- VernacularTitle:改善病情抗风湿药物对类风湿关节炎滑膜差异表达基因的影响
- Author:
Lingjing CHENG
1
;
Shengxiao ZHANG
;
Qi YU
;
Chaoyue ZHENG
;
Shuang FENG
;
Teng KONG
;
Xiangfei SUN
;
Peifeng HE
;
Xuechun LU
Author Information
1. 山西医科大学管理学院，太原 030001
- Keywords:
Arthritis, rheumatoid;
Synovial membrane;
Antirheumatic agents;
Gene expression
- From:
Chinese Journal of Rheumatology
2023;27(8):541-544,C8-4-C8-6,F3
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To identify differentially expressed genes (DEGs) associated with the progression of synovitis in RA by using bioinformatics analysis and explore the effects of DMARDs such as methotrexate, tocilizumab and rituximab on the DEGs in RA synovium.Methods:RA expression profile microarray data GSE7307、GSE12021、GSE55457、GSE55235、GSE77298、GSE89408 were acquired from the public gene chip database (GEO), including 113 synovial tissue samples from RA and 70 healthy controls (HC). At the same time, synovial expression microarrays GSE45867, GSE24742 and GSE97165 after DMARDs treatment were obtained. These data included 8 samples treated with methotrexate, 12 treated with tocilizumab, 12 treated with rituximab and 19 treated with combined tDMARDs. R software was used to screen DEGs and Venn plots using gene ontology function enrichment and Kyoto encyclopedia of genes and genomes pathway enrichment analysis. Hub genes were selected by STRING online analysis tool and Cytoscape software.Results:Compared with HC, 797 DEGs were up-regulated and 434 DEGs were down-regulated in the synovial tissue of RA. These DEGs were mainly enriched in T cell activation, immune response-activating cell surface receptor signaling pathway. Using Cytoscape and cytoHubba to obtain 5 sets of DEGs based on the STRING database model, the degree algorithm screened out 10 hub genes: LCK, SYK, PTPRC, HLA-DRA, LYN, NCAPG, TOP2A, JUN, CXCR4, CCNB1. Methotrexate treatment significantly up-regulated 20 DEGs and down-regulated 30 DEGs. Rituximab treatment up-regulated 100 DEGs and down-regulated 55 DEGs. Tocilizumab treatment up-regulated 91 DEGs and down-regulated 317 DEGs. These altered DEGs were enriched in regulating cell adhesion, leukocyte-cell adhesion, leukocyte transfer, and insulin-like growth factor receptor signaling pathways. It was worth noting that after treatment, a total of 306 high-expressing DEGs were down-regulated, and 36 low-expressing DEGs were up-regulated.Conclusion:LCK, insulin-like growth factor receptor signaling pathway, etc. are the responsible molecular mechanisms and key pivot genes for the occurrence and development of RA, and the treatment of DMARDs, which are closely related to the response of RA to the treatment of DMARDs.
