POS0742 SCREENING AND BIOINFORMATICS ANALYSIS OF HUB GENES AND PATHWAYS FOR PRIMARY SJÖGREN’S SYNDROME BASED ON GEO DATABASE

Background:Primary Sjögren’s syndrome (pSS) is an autoimmune disease that featured as lymphoplasmacytic infiltration of the exocrine glands leading to sicca symptoms1. However, its underlying molecular mechanisms remain elusive.Objectives:This study aims to identify differentially expressed genes (DEGs) and pathways associated with the progression of pSS using bioinformatics analysis and explore its pathogenesis.Methods:The pSS-associated gene chip data set GSE66795 was obtained from the Gene Expression Omnibus (GEO) database, which included 131 cases of fully-phenotyped pSS patients’ whole blood samples and 29 cases of control samples. DEGs were screened Using R software. Online tool Metascape2 was used to make Gene Ontology (GO) and KEGG pathway enrichment. The PPI network was performed using String database. Hub genes were identified by Cytoscape.Results:A total of 108 DEGs were captured, including 101 up-regulated genes and 7 down-regulated genes. GO enrichment showed that these DEGs were primarily enriched in defense response to virus, response to interferon-gamma, regulation of innate immune response, response to interferon-beta, double-stranded RNA binding, response to interferon-alpha. KEGG pathway enrichment analysis showed these DEGs were principally enriched in Influenza A, RIG-I-like receptor signaling pathway, necroptosis, Staphylococcus aureus infection. Finally, 9 hub genes (STAT1, IRF7, OAS2, GBP1, OAS1, IFIT3, IFIH1, OAS3, DDX60) had highest degree value.Conclusion:The findings identified molecular mechanisms and the key hub genes that may involve in the occurrence and development of pSS.References:[1]Francois H, Mariette X. Renal involvement in primary Sjogren syndrome. Nat Rev Nephrol 2016;12(2):82-93. doi: 10.1038/nrneph.2015.174 [published Online First: 2015/11/17].[2]Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 2019;10(1):1523. doi: 10.1038/s41467-019-09234-6 [published Online First: 2019/04/05].Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared

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

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.592490 ◽

2020 ◽

Vol 8 ◽

Author(s):

Jing Luo ◽

Xin Liao ◽

Lihe Zhang ◽

Xin Xu ◽

Senhong Ying ◽

...

Keyword(s):

Early Detection ◽

Roc Curve ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Primary Sjögren’S Syndrome ◽

Primary Sjogren’S Syndrome ◽

Hub Genes ◽

Primary Sjögren's Syndrome ◽

Sjögren‘S Syndrome

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.

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