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Integrative Analysis for Elucidating Transcriptomics Landscapes of Systemic Lupus Erythematosus.

ABSTRACT: Systemic lupus erythematosus (SLE) is a complex and heterogeneous autoimmune disease that the immune system attacks healthy cells and tissues. SLE is difficult to get a correct and timely diagnosis, which makes its morbidity and mortality rate very high. The pathogenesis of SLE remains to be elucidated. To clarify the potential pathogenic mechanism of SLE, we performed an integrated analysis of two RNA-seq datasets of SLE. Differential expression analysis revealed that there were 4,713 and 2,473 differentially expressed genes, respectively, most of which were up-regulated. After integrating differentially expressed genes, we identified 790 common differentially expressed genes (DEGs). Gene functional enrichment analysis was performed and found that common differentially expressed genes were significantly enriched in some important immune-related biological processes and pathways. Our analysis provides new insights into a better understanding of the pathogenic mechanisms and potential candidate markers for systemic lupus erythematosus.

SUBMITTER: Zhang H

PROVIDER: S-EPMC8599929 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Integrative Analysis for Elucidating Transcriptomics Landscapes of Systemic Lupus Erythematosus.

Zhang Haihong H Wang Yanli Y Feng Jinghui J Wang Shuya S Wang Yan Y Kong Weisi W Zhang Zhiyi Z

Frontiers in genetics 20211104

Systemic lupus erythematosus (SLE) is a complex and heterogeneous autoimmune disease that the immune system attacks healthy cells and tissues. SLE is difficult to get a correct and timely diagnosis, which makes its morbidity and mortality rate very high. The pathogenesis of SLE remains to be elucidated. To clarify the potential pathogenic mechanism of SLE, we performed an integrated analysis of two RNA-seq datasets of SLE. Differential expression analysis revealed that there were 4,713 and 2,473 ...[more]

PMID: 34804130

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Project description:BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease with strong heterogeneity, leading to variable clinical symptoms, which makes diagnosis and activity evaluation difficult.MethodsThe original dataset of GSE88884 was analyzed to screen differentially expressed genes (DEGs) of SLE and the correlation between DEGs and clinical parameters (SLEDAI, anti-dsDNA, C3, and C4). The result was validated by microarray GSE121239 and SLE patients with RT-qPCR. Next, receiver operator characteristic (ROC) analysis, correlation analysis, and ordinal logistic regression were applied, respectively, to evaluate the capability of diagnosis and prediction of the candidate biomarker. Subsequently, the biological functions of the candidate biomarker were investigated through KEGG and GO enrichment, protein-protein interaction network, and the correlation matrix.ResultsA total of 283 DEGs were screened, and seven of them were overlapped with SLE-related genes. DDX60 was identified as the candidate biomarker. Analyses of GSE88884, GSE121239, and SLE patients with RT-qPCR indicated that DDX60 expression level is significantly higher in patients with high disease activity. ROC analysis and the area under the ROC curve (AUC = 0.8818) suggested that DDX60 has good diagnostic performance. DDX60 expression level was positively correlated with SLEDAI scores (r = 0.24). For every 1-unit increase in DDX60 expression value, the odds of a higher stage of activity of SLE disease are multiplied by 1.47. The function of DDX60 mainly focuses on IFN-I-induced antiviral activities, RIG-I signaling, and innate immune. Moreover, DDX60 plays a synergistic role with DDX58, IFIH1, OASL, IFIT1, and other related genes in the SLE pathogenesis. Conclusions. DDX60 is differently expressed in SLE, and it is significantly related to both serological indicators and the disease activity of SLE. We suggested that DDX60 might be a potential biomarker for SLE diagnosis and management.

Dataset Information

Integrative Analysis for Elucidating Transcriptomics Landscapes of Systemic Lupus Erythematosus.

Publications

Integrative Analysis for Elucidating Transcriptomics Landscapes of Systemic Lupus Erythematosus.

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