Identification of Candidate Genes Related to Synovial Macrophages in Rheumatoid Arthritis by Bioinformatics Analysis

Xu, Jia; Zhang, Mingying; Jiao, Wei; Hu, Congqi; Wu, Depei; Jia-hui, YU; Chen, Guangxing

doi:10.2147/ijgm.s333512

Cited by 10 publications

(7 citation statements)

References 44 publications

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“…Six datasets were obtained from the Gene Expression Omnibus (GEO) database [ 29 – 33 ], which were all sampled from the synovium. These datasets are detailed in Table 1 .…”

Section: Methodsmentioning

confidence: 99%

[Retracted] Identification of Diagnostic Biomarkers, Immune Infiltration Characteristics, and Potential Compounds in Rheumatoid Arthritis

Chen

Zhao

et al. 2022

BioMed Research International

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Aims. This study is aimed at investigating the pathogenesis of rheumatoid arthritis (RA) by identifying key biomarkers, associated immune infiltration, and small-molecule compounds using bioinformatic analysis. Methods. Six datasets were obtained from the Gene Expression Omnibus database, and the batch effect was adjusted. Functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyse differentially expressed genes (DEGs). Furthermore, candidate small-molecule drugs associated with RA were selected from the Connectivity Map (CMap) database. The least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and multivariate logistic regression analyses were performed on DEGs to screen for RA diagnostic markers. The receiver operating characteristic curve, concordance index, and GiViTi calibration band were the metrics used to assess the diagnostic markers of RA identified in this analysis. The single-sample gene set enrichment analysis was performed to calculate the scores of infiltrating immune cells and evaluate the activities of immune-related pathways. Finally, the correlation between screening markers and RA diagnosis was determined. Results. A total of 227 DEGs were identified. Functional enrichment analysis and KEGG revealed that DEGs were enriched by the immune response. CMap analysis identified 11 small-molecule compounds with therapeutic potential for RA. In gene expression, the activities of 13 immune cells and 12 immune-related pathways significantly differed between patients with RA and healthy controls. DPYSL3 and SPP1 had the potential to diagnose RA. SPP1 expression was positively correlated with DPYSL3 in 11 immune cells and 10 immune-related pathways. Conclusion. This study comprehensively analysed DEGs and immune infiltration and screened for potential diagnostic markers and small-molecule compounds of RA.

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“…Six datasets were obtained from the Gene Expression Omnibus (GEO) database [ 29 – 33 ], which were all sampled from the synovium. These datasets are detailed in Table 1 .…”

Section: Methodsmentioning

confidence: 99%

[Retracted] Identification of Diagnostic Biomarkers, Immune Infiltration Characteristics, and Potential Compounds in Rheumatoid Arthritis

Chen

Zhao

et al. 2022

BioMed Research International

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“…FN-1, an ECM protein produced by fibroblasts, was previously found to be involved in the pathological changes in many tissues ( Liu et al, 2019 ; Baik et al, 2022 ). Furthermore, emerging evidence has revealed that FN-1 is closely related to RA initiation and development ( Przybysz et al, 2007 ; van Beers et al, 2012 ; Xu et al, 2021 ). In recently published studies, a systematic investigation of the functions, pathways, and networks of the genes related to RA was carried out.…”

Section: Discussionmentioning

confidence: 99%

Fibronectin-1 is a dominant mechanism for rheumatoid arthritis via the mediation of synovial fibroblasts activity

Yang

Zhang

Liang

et al. 2022

Front. Cell Dev. Biol.

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Rheumatoid arthritis (RA) has a high incidence and adverse effects on patients, thus posing a serious threat to people’s life and health. However, the underlying mechanisms regarding the development of RA are still elusive. Herein, we aimed to evaluate the RA-associated molecular mechanisms using the scRNA-seq technique. We used the GEO database to obtain scRNA-seq datasets for synovial fibroblasts (SFs) from RA cases, and the genes were then analyzed using principal component analysis (PCA) and T-Stochastic Neighbor Embedding (TSNE) analyses. Bioinformatics evaluations were carried out for asserting the highly enriched signaling pathways linked to the marker genes, and the key genes related to RA initiation were further identified. According to the obtained results, 3 cell types (0, 1, and 2) were identified by TSNE and some marker genes were statistically upregulated in cell type 1 than the other cell types. These marker genes predominantly contributed to extracellular matrix (ECM) architecture, collagen-harboring ECM, and ECM structural components, and identified as enriched with PI3K/AKT signaling cascade. Notably, fibronectin-1 (FN-1) has been identified as a critical gene that is strongly linked to the development of SFs and has enormous promise for regulating the onset of RA. Moreover, such an investigation offers novel perspectives within onset/progression of RA, suggesting that FN-1 may be a key therapeutic target for RA therapies.

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“…A study of esophageal cancer showed that MMP-9 might regulate tumour-associated macrophages ( Yuan et al, 2021 ). Previous studies have shown that MMP-9 and macrophages participate in the pathogenesis of RA ( Xu et al, 2021 ) and OA ( Ostojic et al, 2021 ). Our results indicate that MMP9 is significantly overexpressed.…”

Section: Discussionmentioning

confidence: 99%

Construction and analysis of a lncRNA–miRNA–mRNA competing endogenous RNA network from inflamed and normal synovial tissues after anterior cruciate ligament and/or meniscus injuries

Xiao

Yang²,

Ren³

et al. 2022

Front. Genet.

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Background: Despite ample evidence demonstrating that anterior cruciate ligament (ACL) and meniscus tears are associated with posttraumatic osteoarthritis (PTOA) development, the contributing factors remain unknown. Synovial inflammation has recently been recognized as a pivotal factor in the pathogenesis of OA. However, there is a lack of data on synovial profiles after ACL or meniscus injuries, which may contribute to PTOA.Methods: Twelve patients with ACL tears and/or meniscus injuries were recruited. During surgery, synovial tissues were obtained from the injured knees. The inflammation status of the synovium was characterized according to macroscopic criteria and histological synovitis grades. Then the synovial tissues were classified as control group or inflamed group. High-throughput RNA sequencing of the synovial samples (3 vs. 3) was conducted to identify differentially expressed (DE) RNAs. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein–protein interaction (PPI) analyses were performed to investigate DE mRNAs. Next, competing endogenous RNA (ceRNA) networks were constructed based on bioinformatics analyses. Associations of the identified DE genes (DEGs) with infiltrating immune cells were explored using Pearson correlation analysis.Results: The results showed that 2793 mRNAs, 3392 lncRNAs and 211 miRNAs were significantly DE between two groups. The top 3 significantly upregulated GO terms and KEGG pathways were immune response, adaptive immune response and immune system process, systemic lupus erythematosus, haematopoietic cell lineage and cytokine–cytokine receptor interaction, respectively. In PPI networks, the top 10 hub genes were IL6, CCR7, C3, CCR5, CXCR3, CXCL8, IL2, CCR3, CCR2 and CXCL1. Seven mRNAs (EPHA5, GSN, ORC1, TLN2, SOX6, NKD2 and ADAMTS19), 4 lncRNAs (MIR4435-2HG, TNXA, CEROX1 and TMEM92-AS1) and 3 miRNAs (miR-486-5p, miR-199a-3p and miR-21-3p) were validated by quantitative real-time polymerase chain reaction and sub-networks were constructed. In correlation analysis, MMP9 correlated positively with M0 macrophages and plasma cells, NKD2 positively with CD8 T cells, and CCR7 and IL2RB positively with naive B cells.Conclusion: Our study provides foundational synovial inflammation profiles following knee trauma. The ceRNA and PPI networks provide new insight into the biological processes and underlying mechanisms of PTOA. The differential infiltration profiles of immune cells in synovium may contribute to PTOA development. This study also highlights immune-related DEGs as potential PTOA treatment biomarkers.

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Identification of Candidate Genes Related to Synovial Macrophages in Rheumatoid Arthritis by Bioinformatics Analysis

Cited by 10 publications

References 44 publications

[Retracted] Identification of Diagnostic Biomarkers, Immune Infiltration Characteristics, and Potential Compounds in Rheumatoid Arthritis

[Retracted] Identification of Diagnostic Biomarkers, Immune Infiltration Characteristics, and Potential Compounds in Rheumatoid Arthritis

Fibronectin-1 is a dominant mechanism for rheumatoid arthritis via the mediation of synovial fibroblasts activity

Construction and analysis of a lncRNA–miRNA–mRNA competing endogenous RNA network from inflamed and normal synovial tissues after anterior cruciate ligament and/or meniscus injuries

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