The relationship between Sjögren's syndrome and recurrent pregnancy loss: a bioinformatics analysis

Abstract

Research QuestionSjögren's syndrome (SS) is an autoimmune disease and also an essential factor in recurrent pregnancy loss (RPL). What are the gene-related relationships between SS and RPL pathogenesis? DesignWe obtained the SS- and RPL-related gene datasets from the Gene Expression Omnibus database and identified the co-expression modules and shared differentially expressed genes (DEGs) in diseases through the weighted gene co-expression network analysis (WGCNA) and limma analysis based on sample size. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were applied to reveal the hidden biological pathways. Additionally, shared hub gene identification, gene set enrichment analysis, hub gene's association with ferroptosis and immunity, drug sensitivity analysis, single-cell RNA sequencing analysis, and construction of ceRNA network were conducted. ResultsBy intersecting the genes from the WGCNA and limma analysis, one shared hub gene (KCNN3) was derived, exhibiting upregulation in SS and RPL. There was a positive relationship between KCNN3 and the immune-related gene TLR2. The ceRNA network revealed that XIST was the most shared lncRNA and could competitively bind with 8 miRNAs to regulate the expression of KCNN3. Forty-eight drugs were found to be strongly associated with KCNN3 expression, such as Estramustine and cyclosporine. Moreover, KCNN3 exhibited high expression in RPL endothelial cells of villus tissue. ConclusionsThis research is one of the initial studies to reveal that SS shares common biological pathways with RPL. KCNN3 was identified as the one hub gene correlated with SS and RPL, and it may be a new target for mechanistic studies on SS and RPL.