Identification of Disease-Specific Hub Biomarkers and Immune Infiltration in Osteoarthritis and Rheumatoid Arthritis Synovial Tissues by Bioinformatics Analysis.

Fei Sun,Jian Lin Zhou,Jia Rui Cao,Chen Qiu,Hao Peng,Pu Ji Peng,Shabana Shabana

doi:10.1155/2021/9911184

Abstract

Background Osteoarthritis (OA) and rheumatoid arthritis (RA) are well-known cause of joint disability. Although they have shown the analogous clinical features involving chronic synovitis that progresses to cartilage and bone destruction, the pathogenesis that initiates and perpetuates synovial lesions between RA and OA remains elusive. Objective This study is aimed at identifying disease-specific hub genes, exploring immune cell infiltration, and elucidating the underlying mechanisms associated with RA and OA synovial lesion. Methods Gene expression profiles (GSE55235, GSE55457, GSE55584, and GSE12021) were selected from Gene Expression Omnibus for analysis. Differentially expressed genes (DEGs) were identified by the “LIMMA” package in Bioconductor. The DEGs were identified by Gene Ontology (GO) and KEGG pathway analysis. A protein-protein interaction network was constructed to identify candidate hub genes by using STRING and Cytoscape. Hub genes were identified by validating from GSE12021. Furthermore, we employed the CIBERSORT website to assess immune cell infiltration between OA and RA. Finally, we explored the correlation between the levels of hub genes and relative proportion of immune cells in OA and RA. Results We identified 68 DEGs which were mainly enriched in immune response and chemokine signaling pathway. Six hub genes with a cutoff of AUC > 0.80 by ROC analysis and relative expression of P < 0.05 were identified successfully. Compared with OA, the RA synovial tissues consisted of a higher proportion of 7 immune cells, whereas 4 immune cells were found in relatively lower proportion (P < 0.05). In addition, the levels of 6 hub genes were closely associated with relative proportion of 11 immune cells in OA and RA. Conclusions We used bioinformatics analysis to identify hub genes and explored immune cell infiltration of immune microenvironment in synovial tissues. Our results should offer insights into the underlying molecular mechanisms of synovial lesion and provide potential target for immune-based therapies of OA and RA.

Highlights

Rheumatoid arthritis (RA) affects approximately 1% of the population, has a female : male ratio of 2.5 : 1, and mostly occurs among adults aged 40–70 years [1]
Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that these genes were significantly enriched in the cytokine-cytokine receptor interaction, rheumatoid arthritis, and chemokine signaling pathway (Figure 3(b))
We found that the correlation of expression of CXCL3 and resting dendritic cells was diametrically opposite in OA and rheumatoid arthritis (RA) synovial tissues, which may give insights into immune microenvironment of OA and RA

Summary

Introduction

Rheumatoid arthritis (RA) affects approximately 1% of the population, has a female : male ratio of 2.5 : 1, and mostly occurs among adults aged 40–70 years [1]. Osteoarthritis (OA) and rheumatoid arthritis (RA) are well-known cause of joint disability They have shown the analogous clinical features involving chronic synovitis that progresses to cartilage and bone destruction, the pathogenesis that initiates and perpetuates synovial lesions between RA and OA remains elusive. This study is aimed at identifying diseasespecific hub genes, exploring immune cell infiltration, and elucidating the underlying mechanisms associated with RA and OA synovial lesion. We explored the correlation between the levels of hub genes and relative proportion of immune cells in OA and RA. The levels of 6 hub genes were closely associated with relative proportion of 11 immune cells in OA and RA. We used bioinformatics analysis to identify hub genes and explored immune cell infiltration of immune microenvironment in synovial tissues.

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Discussion

Conclusion