Identification of biomarkers associated with synovitis in rheumatoid arthritis by bioinformatics analyses

Biosci Rep. 2020 Sep 30;40(9):BSR20201713. doi: 10.1042/BSR20201713.

Abstract

Objectives: Rheumatoid arthritis (RA) is the most common inflammatory arthritis in the world, but its underlying mechanism is still unclear. The present study aims to screen and verify the potential biomarkers of RA.

Methods: We searched the Gene Expression Omnibus (GEO) database for synovial expression profiling from different RA microarray studies to perform a systematic analysis. Functional annotation of differentially expressed genes (DEGs) was conducted, including GO enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The protein-protein interaction (PPI) networks of the DEGs were constructed based on data from the STRING database. The expression levels of the hub genes in normal membranes and RA synovium were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot system.

Results: A total of 444 differential expression genes were identified, including 172 up-regulated and 272 down-regulated genes in RA synovium compared with normal controls. The top ten hub genes; protein tyrosine phosphatase receptor type C (PTPRC), LCK proto-oncogene (LCK), cell division cycle 20 (CDC20), Jun proto-oncogene (JUN), cyclin-dependent kinase 1 (CDK1), kinesin family member 11 (KIF11), epidermal growth factor receptor (epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA), mitotic arrest deficient 2 like 1 (MAD2L1), and signal transducer and activator of transcription 1 (STAT1) were identified from the PPI network, and the expression level of VEGFA and EGFR was significantly increased in RA membranes (P<0.05).

Conclusion: Our results indicate that the hub genes VEGFA and EGFR may have essential effects during the development of RA and can be used as potential biomarkers of RA.

Keywords: Rheumatoid arthritis; bioinformatics; hub gene.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / diagnosis*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / surgery
  • Arthroplasty, Replacement, Knee
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Case-Control Studies
  • Computational Biology
  • Datasets as Topic
  • ErbB Receptors / analysis
  • ErbB Receptors / metabolism
  • Female
  • Gene Expression Profiling
  • Humans
  • Knee Joint / immunology
  • Knee Joint / pathology
  • Knee Joint / surgery
  • Male
  • Middle Aged
  • Proto-Oncogene Mas
  • Synovial Membrane / immunology
  • Synovial Membrane / pathology*
  • Synovitis / diagnosis*
  • Synovitis / immunology
  • Synovitis / pathology
  • Synovitis / surgery
  • Tissue Array Analysis
  • Vascular Endothelial Growth Factor A / analysis*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Biomarkers
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • EGFR protein, human
  • ErbB Receptors