Liu Xiaobing, Huang Yake, Zhang Hao, Yang Xia, Liu Quanxing, Dai Jigang
Department of Thoracic Surgery, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
Department of Obstetrics and Gynecology, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
Front Immunol. 2025 May 1;16:1528769. doi: 10.3389/fimmu.2025.1528769. eCollection 2025.
Studies have shown that sialylation of C1 esterase inhibitors is crucial for their interaction with histones, and histone-C1 esterase inhibitor complexes are detected in acute respiratory distress syndrome (ARDS), suggesting a potential role of sialylation in ARDS. However, the specific function of sialylation in ARDS remains unclear. Therefore, this study aimed to investigate the mechanism of sialylation-related genes (SRGs) in sepsis-induced ARDS.
The ARDS related datasets (GSE32707, GSE66890, and GSE151263) were included in this study. Candidate genes were identified by implementing differential expression analysis and weighted gene co-expression network analysis (WGCNA). Subsequently, further selection by machine learning and expression assessment confirmed the key genes related to sialylation in sepsis-induced ARDS. Following this, the predictive ability of key genes as a whole for sepsis-induced ARDS was evaluated by creating a nomogram model. Afterwards, enrichment analysis, construction of regulatory networks, and drug prediction analysis were implemented to further understand the molecular mechanisms of action of key genes. Furthermore, single-cell RNA sequencing (scRNA-seq) data analysis was conducted to obtain key cells. Additionally, cell communication and pseudo-time analyses were implemented. In the end, the expression levels of the key genes were assessed by collecting clinical samples.
CD19 and GPR65 were identified as key genes associated with sialylation in sepsis-induced ARDS. The constructed nomogram model demonstrated that CD19 and GPR65 as a whole exhibited robust predictive capability for sepsis-induced ARDS. Meanwhile, CD19 and GPR65 were also found to be significantly co-enriched in the apoptosis and B-cell receptor signaling pathway. In addition, some important regulators and drugs with targeting effects on key genes were predicted, such as NEAT1, OIP5-AS1, alprostadil, and tacrolimus. Further, the scRNA-seq data analysis identified nine cell types, among which CD14 monocytes (CD14Mono) was designated as the key cell. Importantly, GPR65 expression exhibited dynamic changes during differentiation of CD14Mono. Also, we found that CD19 was significantly up-regulated in ARDS group.
We identified CD19 and GPR65 as key genes associated with sialylation in sepsis-induced ARDS, highlighting CD14Mono as key cell type implicated in sepsis-induced ARDS. These findings offered theoretical support for understanding the mechanism of sialylation on sepsis-induced ARDS.
研究表明，C1酯酶抑制剂的唾液酸化对于其与组蛋白的相互作用至关重要，并且在急性呼吸窘迫综合征（ARDS）中检测到组蛋白 - C1酯酶抑制剂复合物，这表明唾液酸化在ARDS中可能发挥作用。然而，唾液酸化在ARDS中的具体功能仍不清楚。因此，本研究旨在探讨唾液酸化相关基因（SRGs）在脓毒症诱导的ARDS中的作用机制。
本研究纳入了ARDS相关数据集（GSE32707、GSE66890和GSE151263）。通过实施差异表达分析和加权基因共表达网络分析（WGCNA）来鉴定候选基因。随后，通过机器学习进一步筛选和表达评估确定了脓毒症诱导的ARDS中与唾液酸化相关的关键基因。在此之后，通过创建列线图模型评估关键基因整体对脓毒症诱导的ARDS的预测能力。之后，进行富集分析、调控网络构建和药物预测分析，以进一步了解关键基因的分子作用机制。此外，进行单细胞RNA测序（scRNA-seq）数据分析以获得关键细胞。另外，实施细胞通讯和伪时间分析。最后，通过收集临床样本评估关键基因的表达水平。
CD19和GPR65被确定为脓毒症诱导的ARDS中与唾液酸化相关的关键基因。构建的列线图模型表明，CD19和GPR65整体对脓毒症诱导的ARDS具有强大的预测能力。同时，还发现CD19和GPR65在细胞凋亡和B细胞受体信号通路中显著共富集。此外，预测了一些对关键基因具有靶向作用的重要调节因子和药物，如NEAT1、OIP5-AS1、前列地尔和他克莫司。进一步地，scRNA-seq数据分析确定了9种细胞类型，其中CD14单核细胞（CD14Mono）被指定为关键细胞。重要的是，GPR65表达在CD14Mono分化过程中表现出动态变化。此外，我们发现ARDS组中CD19显著上调。
我们确定CD19和GPR65为脓毒症诱导的ARDS中与唾液酸化相关的关键基因，突出了CD14Mono作为脓毒症诱导的ARDS中的关键细胞类型。这些发现为理解唾液酸化对脓毒症诱导的ARDS的作用机制提供了理论支持。
