Department of Rheumatology and Immunology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Front Immunol. 2023 Apr 18;14:1150828. doi: 10.3389/fimmu.2023.1150828. eCollection 2023.
Neutrophil extracellular traps (NETs) is an important process involved in the pathogenesis of systemic lupus erythematosus (SLE), but the potential mechanisms of NETs contributing to SLE at the genetic level have not been clearly investigated. This investigation aimed to explore the molecular characteristics of NETs-related genes (NRGs) in SLE based on bioinformatics analysis, and identify associated reliable biomarkers and molecular clusters. Dataset GSE45291 was acquired from the Gene Expression Omnibus repository and used as a training set for subsequent analysis. A total of 1006 differentially expressed genes (DEGs) were obtained, most of which were associated with multiple viral infections. The interaction of DEGs with NRGs revealed 8 differentially expressed NRGs (DE-NRGs). The correlation and protein-protein interaction analyses of these DE-NRGs were performed. Among them, HMGB1, ITGB2, and CREB5 were selected as hub genes by random forest, support vector machine, and least absolute shrinkage and selection operator algorithms. The significant diagnostic value for SLE was confirmed in the training set and three validation sets (GSE81622, GSE61635, and GSE122459). Additionally, three NETs-related sub-clusters were identified based on the hub genes' expression profiles analyzed by unsupervised consensus cluster assessment. Functional enrichment was performed among the three NETs subgroups, and the data revealed that cluster 1 highly expressed DEGs were prevalent in innate immune response pathways while that of cluster 3 were enriched in adaptive immune response pathways. Moreover, immune infiltration analysis also revealed that innate immune cells were markedly infiltrated in cluster 1 while the adaptive immune cells were upregulated in cluster 3. As per our knowledge, this investigation is the first to explore the molecular characteristics of NRGs in SLE, identify three potential biomarkers (HMGB1, ITGB2, and CREB5), and three distinct clusters based on these hub biomarkers.
中性粒细胞胞外诱捕网（NETs）是系统性红斑狼疮（SLE）发病机制中的一个重要过程，但 NETs 在遗传水平上导致 SLE 的潜在机制尚未得到明确研究。本研究旨在基于生物信息学分析探讨 SLE 中与 NETs 相关的基因（NRGs）的分子特征，并确定相关的可靠生物标志物和分子聚类。从基因表达综合数据库中获取数据集 GSE45291 并将其用作后续分析的训练集。共获得 1006 个差异表达基因（DEGs），其中大多数与多种病毒感染有关。DEGs 与 NRGs 的相互作用揭示了 8 个差异表达的 NRGs（DE-NRGs）。对这些 DE-NRGs 进行了相关性和蛋白质-蛋白质相互作用分析。其中，HMGB1、ITGB2 和 CREB5 通过随机森林、支持向量机和最小绝对值收缩和选择算子算法被选为枢纽基因。在训练集和三个验证集中（GSE81622、GSE61635 和 GSE122459）均证实了这些基因对 SLE 的诊断具有显著价值。此外，还根据枢纽基因的表达谱通过无监督共识聚类评估确定了三个与 NETs 相关的亚群。对三个 NETs 亚群进行了功能富集分析，结果表明，簇 1 中高表达的 DEGs 主要存在于固有免疫反应途径中，而簇 3 中则富集于适应性免疫反应途径。此外，免疫浸润分析还表明，簇 1 中固有免疫细胞显著浸润，而簇 3 中适应性免疫细胞上调。据我们所知，这是首次探索 SLE 中 NRGs 的分子特征，确定三个潜在的生物标志物（HMGB1、ITGB2 和 CREB5）以及基于这些枢纽生物标志物的三个不同聚类。
Zotero 插件
