Abstract
Purpose: Sjögren’s syndrome (SS) is an autoimmune disease characterized by dry mouth and eyes. To date, the exact molecular mechanisms of its etiology are still largely unknown. The aim of this study was to identify SS related key genes and functionally enriched pathways using the weighted gene co-expression network analysis (WGCNA).Materials and Methods: We downloaded the microarray data of 190 SS patients and 32 controls from Gene Expression Omnibus (GEO). Gene network was constructed and genes were classified into different modules using WGCNA. In addition, for the hub genes in the most related module to SS, gene ontology analysis was applied. The expression profile and diagnostic capacity (ROC curve) of interested hub genes were verified using a dataset from the GEO. Moreover, gene set enrichment analysis (GSEA) was also performed.Results: A total of 1483 differentially expressed genes were filtered. Weighted gene coexpression network was constructed and genes were classified into 17 modules. Among them, the turquoise module was most closely associated with SS, which contained 278 genes. These genes were significantly enriched in 10 Gene Ontology terms, such as response to virus, immune response, defense response, response to cytokine stimulus, and the inflammatory response. A total of 19 hub genes (GBP1, PARP9, EPSTI1, LOC400759, STAT1, STAT2, IFIH1, EIF2AK2, TDRD7, IFI44, PARP12, FLJ20035, PARP14, ISGF3G, XAF1, RSAD2,LY6E, IFI44L, and DDX58) were identified. The expression levels of the five interested genes including EIF2AK2, GBP1, PARP12, PARP14, and TDRD7 were also confirmed. ROC curve analysis determined that the above five genes’ expression can distinguish SS from controls (the area under the curve is all greater than 0.7). GSEA suggests that the SS samples with highly expressed EIF2AK2 or TDRD7 genes are correlated with inflammatory response, interferon α response, and interferon γ response.Conclusion: The present study applied WGCNA to generate a holistic view of SS and provide a basis for the identification of potential pathways and hub genes that may be involved in the development of SS.
Highlights
Sjögren’s syndrome (SS), a systemic autoimmune disease, is characterized by lymphocyte infiltration in exocrine glands, which further leads to destruction of their function (Fox, 2005)
Through gene set enrichment analysis, we found the full list of gene sets enriched in samples with EIF2AK2 (Figure 8A), GBP1 (Figure 8B), PARP12 (Figure 8C), PARP14 (Figure 8D), or TDRD7 (Figure 8E) highly expressed
Through Weighted gene co-expression network analysis (WGCNA) method, we constructed SS-related gene co-expression networks, and found several key gene co-expression modules and several hub genes related to the pathogenesis of SS
Summary
Sjögren’s syndrome (SS), a systemic autoimmune disease, is characterized by lymphocyte infiltration in exocrine glands, which further leads to destruction of their function (Fox, 2005). SS is clinically characterized by keratoconjunctivitis sicca (dry eyes) and xerostomia (dry mouth) and may be accompanied by multi-organ systemic manifestations (Fox, 9482). SS that occurs without any other autoimmune diseases was defined as primary Sjögren’s syndrome (pSS) (Molano-Gonzalez et al, 2018). SS can occur in association with other autoimmune diseases, such as autoimmune thyroid diseases (AITD), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) (Salliot et al, 2007; Anaya et al, 2016; Alani et al, 2018). To our best knowledge, the etiology and progression of SS are still unclear to date
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