Open Access

Identification of key candidate genes and biological pathways in the synovial tissue of patients with rheumatoid arthritis

  • Authors:
    • Feng Yu
    • Guanghui Hu
    • Lei Li
    • Bo Yu
    • Rui Liu
  • View Affiliations

  • Published online on: April 4, 2022     https://doi.org/10.3892/etm.2022.11295
  • Article Number: 368
  • Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to identify potential key candidate genes and mechanisms associated with rheumatoid arthritis (RA). Gene expression data from GSE55235, GSE55457 and GSE1919 datasets were downloaded from the Gene Expression Omnibus database. These datasets comprised 78 tissue samples collectively, including 25 healthy synovial membrane samples and 28 RA synovial membrane samples, whilst the 25 osteoarthritis (OA) samples were not included in the analysis. The differentially expressed genes (DEGs) between the two types of samples were identified with the Linear Models for Microarray Analysis package in R. Gene Ontology (GO) functional term and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analyses were also performed. In addition, Protein‑Protein Interaction (PPI) network and module analyses were visualized using Cytoscape, and subsequent hub gene identification as well as GO and KEGG enrichment analyses of the modules was performed. Finally, reverse transcription‑quantitative PCR (RT‑qPCR) was used to validate the expression of the DEGs identified by GO and KEGG analysis in vitro. The analysis identified 491 DEGs, including 289 upregulated and 202 downregulated genes, which were mainly enriched in the following pathways: ‘Cytokine‑cytokine receptor interaction’, ‘Rheumatoid arthritis’, ‘Chemokine signaling pathway’, ‘Intestinal immune network for IgA production’ and ‘Primary immunodeficiency’. The top 10 hub genes identified from the PPI network were IL‑6, protein tyrosine phosphatase receptor type C, VEGFA, CD86, EGFR, C‑X‑C chemokine receptor type 4, matrix metalloproteinase 9, CC‑chemokine receptor type (CCR)7, CCR5 and selectin L. KEGG signaling pathway enrichment analysis of the top two modules identified from the PPI network revealed that the genes in Module 1 were mainly enriched in the ‘Cytokine‑cytokine receptor interaction’ and ‘Chemokine signaling pathway’, whereas analysis of Module 2 revealed that the genes were mainly enriched in ‘Primary immunodeficiency’ and ‘Cytokine‑cytokine receptor interaction’. Finally, the results of the RT‑qPCR and western blot analysis demonstrated that the expression levels of inflammation and NF‑κB signaling pathway‑related mRNAs were significantly upregulated following lipopolysaccharide stimulation. In conclusion, the findings of the present study identified key genes and signaling pathways associated with RA, which may improve the current understanding of the molecular mechanisms underlying its development and progression. The identified hub genes may also be used as potential targets for RA diagnosis and treatment.
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June-2022
Volume 23 Issue 6

Print ISSN: 1792-0981
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Spandidos Publications style
Yu F, Hu G, Li L, Yu B and Liu R: Identification of key candidate genes and biological pathways in the synovial tissue of patients with rheumatoid arthritis. Exp Ther Med 23: 368, 2022
APA
Yu, F., Hu, G., Li, L., Yu, B., & Liu, R. (2022). Identification of key candidate genes and biological pathways in the synovial tissue of patients with rheumatoid arthritis. Experimental and Therapeutic Medicine, 23, 368. https://doi.org/10.3892/etm.2022.11295
MLA
Yu, F., Hu, G., Li, L., Yu, B., Liu, R."Identification of key candidate genes and biological pathways in the synovial tissue of patients with rheumatoid arthritis". Experimental and Therapeutic Medicine 23.6 (2022): 368.
Chicago
Yu, F., Hu, G., Li, L., Yu, B., Liu, R."Identification of key candidate genes and biological pathways in the synovial tissue of patients with rheumatoid arthritis". Experimental and Therapeutic Medicine 23, no. 6 (2022): 368. https://doi.org/10.3892/etm.2022.11295