Identifying Key Genes and Functionally Enriched Pathways in Sjögren’s Syndrome by Weighted Gene Co-Expression Network Analysis

Yao, Qiuming; Song, Zhenyu; Wang, Bin; Qin, Qiu; Zhang, Jinan

doi:10.3389/fgene.2019.01142

Cited by 66 publications

(58 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, WGCNA has been applied to construct gene co-expression network modules and identify hub genes in several autoimmune diseases, including rheumatoid arthritis (RA) (Ma et al, 2017), inflammatory bowel disease (IBD) (Li et al, 2016), and autoimmune thyroid disease (ATD) (Shao et al, 2018). Moreover, the gene expression profiles of more than 200 PBMC samples of pSS have been investigated, and WGCNA analysis was applied to explore the gene-network signature and potential functions of hub genes based on Gene Expression Omnibus (GEO) public database (Yao et al, 2019). Recently, Inamo et al (2020) also identified LINC00487 and SOX4 as key genes associated with the dysregulation of B cells in pSS patients using WGCNA algorithm.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome Sequencing Reveals Potential Roles of ICOS in Primary Sjögren’s Syndrome

Luo

Liao

Zhang

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease characterized by exocrine gland damage and extraglandular involvements. To identify potential biomarkers for the early detection of pSS and to further investigate the potential roles of the biomarkers in the progression of pSS, our previous RNA sequencing data and four microarray data of salivary glands (SGs) were combined for integrative transcriptome analysis between pSS and non-pSS. Differential gene expression analysis, gene co-expression network analysis, and pathway analysis were conducted to detect hub genes, which were subsequently investigated in peripheral blood mononuclear cell (PBMC) and plasma. Correlation analysis, single-gene Gene Set Enrichment Analysis, and receiver operating characteristic (ROC) curve were applied to investigate the potential function of the hub genes and their classification capacity for pSS. A total of 51 common up-regulated genes were identified among different pSS cohorts. A key module was found to be the most closely linked to pSS, which was significantly associated with inflammation-related pathways. Seven overlapped hub genes (ICOS, SELL, CR2, BANK1, MS4A1, ZC3H12D, and CCR7) were identified, among which ICOS was demonstrated to be involved in most crucial immune pathways. ICOS was up-regulated not only in SGs but also in PBMC and plasma in pSS, and the expression of ICOS was closely associated with lymphocytic infiltration in SGs and disease activity of pSS patients. It showed a strong classification capacity with classic clinical index in SGs (ROC curve 0.9821) and significant distinct discrimination in PBMC (ROC curve 0.9107). These findings are expected to gain a further insight into the pathogenesis of pSS and provide a promising candidate for the early detection of pSS.

show abstract

Section: Introductionmentioning

confidence: 99%

Transcriptome Sequencing Reveals Potential Roles of ICOS in Primary Sjögren’s Syndrome

Luo

Liao

Zhang

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Type I IFN may therefore inhibit XIAP function by the induction of XAF1, and then negatively regulate the inhibitor of apoptosis. XAF1 was upregulated in whole peripheral blood from the Sjögren's syndrome patients compared with controls [46]. However, there have been no research about the role of XAF1 in SLE/LN progression.…”

Section: Discussionmentioning

confidence: 90%

XAF1 is identified as a novel hub gene and associated with the clinical characteristics of lupus nephritis

Zeng¹,

Xie²,

Sun³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) that is the most common cause of morbidity and mortality. At present, the definitive therapies towards LN remains to be elucidated, so illuminating the molecular mechanism behind the disease has become an urgent task for researchers. This study set out to screen the hub genes of LN. Methods The microarray expression profile dataset GSE32591 from the Gene Expression Omnibus (GEO) database with 15 normal and 32 LN samples was assessed in this study. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the LN-related differentially expressed genes (DEGs). The Nephroseq database was performed to identify correlation analysis between unexplored hub genes and clinical features of LN. Additionally, the expression of the candidate genes was detected in the kidney tissue by immunohistochemistry. Results The 14 genes (13 upregulated and 1 downregulated) ultimately screened out as candidate hub genes of the pathogenesis of LN. Moreover, Correlation analysis between the unexplored hub genes and clinical features of LN suggested that XAF1 may involve in the progression of LN. Finally, our data demonstrated that the expression level of XAF1 was upregulated in LN compared with IgA nephropathy (IgAN) and related to the WHO Lupus Nephritis Class and the quantitative 24 h proteinuria of LN patients. Conclusions The current study proposed XAF1 as a novel hub gene in LN which may perform as a brand-new biomarker or therapeutic target of LN in the future.

show abstract

“…Most immune cell types express cytosolic RNA-sensing receptors and their downstream signaling molecules at steady state [ 112 ]. Considering that the RNA-sensing receptors themselves are IFN-regulated, it is not surprising to see increased gene expression of IFIH1/MDA5 , DDX58/RIG-I , EIF2AK2/PKR, and OAS in whole blood and specific leukocyte subsets from pSS patients [ 62 , 64 , 66 , 118 , 119 , 120 , 121 ]. Studies detecting active signaling and functional properties of these pathways in pSS cells have been very limited so far.…”

Section: Cytosolic Ifn-inducing Rna-sensing Pathways In Primary Sjmentioning

confidence: 99%

Making Sense of Intracellular Nucleic Acid Sensing in Type I Interferon Activation in Sjögren’s Syndrome

Huijser

Versnel

2021

JCM

View full text Add to dashboard Cite

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune rheumatic disease characterized by dryness of the eyes and mucous membranes, which can be accompanied by various extraglandular autoimmune manifestations. The majority of patients exhibit persistent systemic activation of the type I interferon (IFN) system, a feature that is shared with other systemic autoimmune diseases. Type I IFNs are integral to anti-viral immunity and are produced in response to stimulation of pattern recognition receptors, among which nucleic acid (NA) receptors. Dysregulated detection of endogenous NAs has been widely implicated in the pathogenesis of systemic autoimmune diseases. Stimulation of endosomal Toll-like receptors by NA-containing immune complexes are considered to contribute to the systemic type I IFN activation. Accumulating evidence suggest additional roles for cytosolic NA-sensing pathways in the pathogenesis of systemic autoimmune rheumatic diseases. In this review, we will provide an overview of the functions and signaling of intracellular RNA- and DNA-sensing receptors and summarize the evidence for a potential role of these receptors in the pathogenesis of pSS and the sustained systemic type I IFN activation.

show abstract

Identifying Key Genes and Functionally Enriched Pathways in Sjögren’s Syndrome by Weighted Gene Co-Expression Network Analysis

Cited by 66 publications

References 35 publications

Transcriptome Sequencing Reveals Potential Roles of ICOS in Primary Sjögren’s Syndrome

Transcriptome Sequencing Reveals Potential Roles of ICOS in Primary Sjögren’s Syndrome

XAF1 is identified as a novel hub gene and associated with the clinical characteristics of lupus nephritis

Making Sense of Intracellular Nucleic Acid Sensing in Type I Interferon Activation in Sjögren’s Syndrome

Contact Info

Product

Resources

About