Weighted gene co-expression network analysis reveals specific modules and hub genes related to immune infiltration of osteoarthritis

Cao, Jingjie; Ding, Han‐Fei; Shang, Jun; Ma, Lei; Wang, Qi; Feng, Shiqing

doi:10.21037/atm-21-4566

Cited by 11 publications

(7 citation statements)

References 51 publications

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“…In this study, we detected those macrophages and most other immune cells were highly infiltrated in the OA synovium. Previous histology-based studies have also demonstrated macrophage enrichment in OA ( 28 , 29 ). Due to their essential roles in immune recruitment, inflammatory damage, and ECM degradation, macrophages have received much attention and are thought to be important lesion driver immune cells in OAs.…”

Section: Discussionmentioning

confidence: 78%

Six macrophage-associated genes in synovium constitute a novel diagnostic signature for osteoarthritis

Liu

Han

et al. 2022

Front. Immunol.

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BackgroundSynovial macrophages play important roles in the formation and progression of osteoarthritis (OA). This study aimed to explore the biological and clinical significance of macrophage-associated genes (MAGs) in OA.MethodsThe OA synovial gene expression profiles GSE89408 and GSE82107 were obtained from the GEO database. Single-sample gene set enrichment analysis (ssGSEA) and GSEA were employed to decipher differences in immune infiltration and macrophage-associated biological pathways, respectively. Protein–protein interaction (PPI) network analysis and machine learning were utilized to establish a macrophage-associated gene diagnostic signature (MAGDS). RT-qPCR was performed to test the expression of key MAGs in murine models.ResultsOA synovium presented high levels of immune infiltration and activation of macrophage-associated biological pathways. A total of 55 differentially expressed MAGs were identified. Using PPI analysis and machine learning, a MAGDS consisting of IL1B, C5AR1, FCGR2B, IL10, IL6, and TYROBP was established for OA diagnosis (AUC = 0.910) and molecular pathological evaluation. Patients with high MAGDS scores may possess higher levels of immune infiltration and expression of matrix metalloproteinases (MMPs), implying poor biological alterations. The diagnostic value of MAGDS was also validated in an external cohort (AUC = 0.886). The expression of key MAGs was validated in a murine model using RT-qPCR. Additionally, a competitive endogenous RNA network was constructed to reveal the potential posttranscriptional regulatory mechanisms.ConclusionsWe developed and validated a MAGDS model with the ability to accurately diagnose and characterize biological alterations in OA. The six key MAGs may also be latent targets for immunoregulatory therapy.

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Section: Discussionmentioning

confidence: 78%

Six macrophage-associated genes in synovium constitute a novel diagnostic signature for osteoarthritis

Liu

Han

et al. 2022

Front. Immunol.

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“…Currently, with the rapid development of computational algorithms and gene chip technology, many researchers have focused on exploring biomarkers of numerous diseases by application of multiple bioinformatic approaches, which enables in-depth analysis of the whole genome and accelerates the progression of disease study. However, many studies are confronted with limited databases (Gao et al, 2019;Cao et al, 2021;Qin et al, 2021), lack of experimental validation (Gao et al, 2019;Zhang et al, 2020b;Cao et al, 2021), controversial methodology validation (Qin et al, 2021;Li et al, 2022), and unconvincing outcomes. Frontiers in Genetics frontiersin.org chondrocytes (Li et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

“…Frontiers in Genetics frontiersin.org chondrocytes (Li et al, 2022). Other research groups also only chose one dataset for WGCNA analysis, and many of them lacked validation experiments (Gao et al, 2019;Zhang et al, 2020b;Cao et al, 2021;Wang et al, 2022) or lacked synoviocyte validation data (Qin et al, 2021;Li et al, 2022). None of them verified and evaluated the diagnostic efficacy of candidate markers by mathematical models.…”

Section: Discussionmentioning

confidence: 99%

Identification of susceptibility modules and hub genes of osteoarthritis by WGCNA analysis

et al. 2022

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Osteoarthritis (OA) is a major cause of pain, disability, and social burden in the elderly throughout the world. Although many studies focused on the molecular mechanism of OA, its etiology remains unclear. Therefore, more biomarkers need to be explored to help early diagnosis, clinical outcome measurement, and new therapeutic target development. Our study aimed to retrieve the potential hub genes of osteoarthritis (OA) by weighted gene co-expression network analysis (WGCNA) and assess their clinical utility for predicting OA. Here, we integrated WGCNA to identify novel OA susceptibility modules and hub genes. In this study, we first selected 477 and 834 DEGs in the GSE1919 and the GSE55235 databases, respectively, from the Gene Expression Omnibus (GEO) website. Genes with p-value<0.05 and | log2FC | > 1 were included in our analysis. Then, WGCNA was conducted to build a gene co-expression network, which filtered out the most relevant modules and screened out 23 overlapping WGCNA-derived hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses elucidated that these hub genes were associated with cell adhesion molecules pathway, leukocyte activation, and inflammatory response. In addition, we conducted the protein–protein interaction (PPI) network in 23 hub genes, and the top four upregulated hub genes were sorted out (CD4, SELL, ITGB2, and CD52). Moreover, our nomogram model showed good performance in predicting the risk of OA (C-index = 0.76), and this model proved to be efficient in diagnosis by ROC curves (AUC = 0.789). After that, a single-sample gene set enrichment (ssGSEA) analysis was performed to discover immune cell infiltration in OA. Finally, human primary synoviocytes and immunohistochemistry study of synovial tissues confirmed that those candidate genes were significantly upregulated in the OA groups compared with normal groups. We successfully constructed a co-expression network based on WGCNA and found out that OA-associated susceptibility modules and hub genes, which may provide further insight into the development of pre-symptomatic diagnosis, may contribute to understanding the molecular mechanism study of OA risk genes.

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“…High‐throughput sequencing technologies are increasingly used in tumor genomics and can also provide insights into nontumor diseases. Bioinformatics analysis has been shown to discover potential early diagnostic biomarkers for osteoarthritis (Cao et al, 2021 ). However, there is little research about TMJD on the gene expression profile and the biological pathways to explore critical signaling pathways and some essential hub genes for the process, complication, and further development of TMJD.…”

Section: Introductionmentioning

confidence: 99%

Integrated bioinformatics analysis of differentially expressed genes in the temporomandibular joint internal derangement

Yang

2023

Clinical & Exp Dental Res

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ObjectivesThis study aimed to identify significant mechanisms and potential treatments for temporomandibular joint internal derangement (TMJD) through integrated bioinformatics analysis.Materials and MethodsGene expression data sets (GSE66864) from the Gene Expression Omnibus (GEO) database were downloaded. Differentially expressed genes (DEGs) were identified both in the treatment groups and in controls by R packages. Network analysis of protein–protein interaction (PPI) and Human Protein Atlas was used to explore DEGs' potential function. DGIdb database was utilized to gain potential drug targets.ResultsIn conclusion, 126 DEGs were selected for TMJD through bioinformatics analysis. Both GO and Kyoto Encyclopedia of Genes and Genomes analyses combined showed the pathways involved in TMJD. A PPI network was constructed to select the top 10 hub genes, of which five hub genes were chosen for further investigation. Moreover, the microenvironment of immune cells related to hub genes was evaluated by R packages. Macrophages play an important role in inflammation and oral‐related tumors. The Human Protein Atlas analysis indicated that the five hub genes are highly related to head and neck cancer. Finally, eight potential drugs were selected for two genes using the DGIdb database.ConclusionOur integrated bioinformatics analysis identified DEGs in TMJD and provided potential ideas for further research and treatment approaches. However, experimental validation of the hub genes and potential drug targets is still needed. The key mechanisms of the identified genes and their potential roles as biomarkers or drug targets in TMJD require further investigation.

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Weighted gene co-expression network analysis reveals specific modules and hub genes related to immune infiltration of osteoarthritis

Cited by 11 publications

References 51 publications

Six macrophage-associated genes in synovium constitute a novel diagnostic signature for osteoarthritis

Six macrophage-associated genes in synovium constitute a novel diagnostic signature for osteoarthritis

Identification of susceptibility modules and hub genes of osteoarthritis by WGCNA analysis

Integrated bioinformatics analysis of differentially expressed genes in the temporomandibular joint internal derangement

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