基于整合生物信息学和单细胞 RNA-seq 分析探讨系统性红斑狼疮和原发性干燥综合征之间的共享分子机制。

BACKGROUND: Systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) are common systemic autoimmune diseases that share a wide range of clinical manifestations and serological features. This study investigates genes, signaling pathways, and transcription factors (TFs) shared between SLE and pSS. METHODS: Gene expression profiles of SLE and pSS were obtained from the Gene Expression Omnibus (GEO). Weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis were conducted to identify shared genes related to SLE and pSS. Overlapping genes were then subject to Gene Ontology (GO) and protein-protein interaction (PPI) network analyses. Cytoscape plugins cytoHubba and iRegulon were subsequently used to screen shared hub genes and predict TFs. In addition, gene set variation analysis (GSVA) and CIBERSORTx were used to calculate the correlations between hub genes and immune cells as well as related pathways. To confirm these results, hub genes and TFs were verified in microarray and single-cell RNA sequencing (scRNA-seq) datasets. RESULTS: Following WGCNA and limma analysis, 152 shared genes were identified. These genes were involved in interferon (IFN) response and cytokine-mediated signaling pathway. Moreover, we screened six shared genes, namely and , out of which three genes, namely and were found to be highly expressed in both microarray and scRNA-seq datasets. IFN response and ITGB2 signaling pathway were identified as potentially relevant pathways. In addition, STAT1 and IRF7 were identified as common TFs in both diseases. CONCLUSION: This study revealed and as the shared genes and identified STAT1 and IRF7 as the common TFs of SLE and pSS. Notably, the IFN response and ITGB2 signaling pathway played vital roles in both diseases. Our study revealed common pathogenetic characteristics of SLE and pSS. The particular roles of these pivotal genes and mutually overlapping pathways may provide a basis for further mechanistic research.

背景：系统性红斑狼疮（SLE）和原发性干燥综合征（pSS）是常见的系统性自身免疫性疾病，具有广泛的临床表现和血清学特征。本研究探讨了 SLE 和 pSS 之间共享的基因、信号通路和转录因子（TFs）。

方法：从基因表达综合数据库（GEO）中获取 SLE 和 pSS 的基因表达谱。进行加权基因共表达网络分析（WGCNA）和差异表达基因（DEG）分析，以识别与 SLE 和 pSS 相关的共享基因。然后对重叠基因进行基因本体论（GO）和蛋白质-蛋白质相互作用（PPI）网络分析。随后使用 Cytoscape 插件 cytoHubba 和 iRegulon 筛选共享枢纽基因并预测 TFs。此外，还使用基因集变异分析（GSVA）和 CIBERSORTx 计算枢纽基因与免疫细胞及相关通路之间的相关性。为了验证这些结果，在微阵列和单细胞 RNA 测序（scRNA-seq）数据集上验证了枢纽基因和 TFs。

结果：通过 WGCNA 和 limma 分析，确定了 152 个共享基因。这些基因参与干扰素（IFN）反应和细胞因子介导的信号通路。此外，我们筛选出 6 个共享基因，即和，其中 3 个基因，即、和，在微阵列和 scRNA-seq 数据集中均高度表达。IFN 反应和 ITGB2 信号通路被认为是潜在相关的通路。此外，STAT1 和 IRF7 被鉴定为两种疾病的共同 TFs。

结论：本研究揭示了和作为共享基因，并确定了 STAT1 和 IRF7 是 SLE 和 pSS 的共同 TFs。值得注意的是，IFN 反应和 ITGB2 信号通路在两种疾病中均发挥着重要作用。本研究揭示了 SLE 和 pSS 的共同发病特征。这些关键基因和相互重叠的通路的特定作用可能为进一步的机制研究提供基础。