【摘要】 目的：解析外周血单个核细胞（PBMC）在脓毒症中的关键靶点及作用机制。方法：从GEO数据库下载GSE205672数据集，包含284例健康对照（HC）和125例脓毒症（SEP）PBMC样本。通过差异表达分析（FDR<0.05,|log₂FC|>0.5）筛选差异表达基因（DEGs）,并进行GO、KEGG和GSEA富集分析。采用加权基因共表达网络分析（WGCNA）构建共表达网络，识别与脓毒症最相关的基因模块。联合Lasso回归、随机森林（RF）和支持向量机递归特征消除（SVM-RFE）筛选核心基因，并以ROC曲线（AUC>0.8）评估其诊断效能。最后，通过CIBERSORT进行免疫细胞浸润分析，验证核心基因与免疫细胞的相关性。结果：共筛选出1 187个脓毒症PBMC相关DEGs,包含447个上调和740个下调。GO和KEGG分析显示，上调DEGs富集于髓系白细胞激活、中性粒细胞胞外诱捕网形成等通路；下调DEGs富集于T细胞分化、冠状病毒病相关通路。WGCNA鉴定出17个模块，其中pink模块与脓毒症相关性最高（r=0.82,P<0.001）。通过联合Lasso回归模型、RF和SVM-RFE分析，最终筛选出2个核心基因：FAM20A和C1QB,二者均为上调DEGs,且ROC分析显示其AUC分别为0.969和0.957,具有显著诊断价值。免疫浸润分析表明，SEP组单核细胞浸润增加（P<0.05）,而CD8⁺T细胞、静息CD4⁺T细胞和静息NK细胞浸润减少（P<0.05）,且与核心基因中免疫细胞浸润情况相符合。结论：PBMC通过调控炎症和免疫失衡参与脓毒症进展，FAM20A和C1QB可能是PBMC在脓毒症中的关键作用靶点。更多还原

【Abstract】 Objective:To clarify the key targets and mechanism of action of peripheral blood mononuclear cells（PBMC）in sepsis.Methods:The GSE205672 dataset from the GEO database was downloaded, which included 284 healthy control（HC）samples and 125 sepsis（SEP）PBMC samples.Differential expression analysis（FDR<0.05,|log₂FC|>0.5）was used to screen differentially expressed genes（DEGs）,and GO,KEGG,and GSEA enrichment analyses were conducted.A co-expression network was constructed using Weighted gene co-expression network analysis（WGCNA） to identify the most relevant gene modules to sepsis.Core genes were selected by Lasso regression, random forest（RF）,and support vector machine-recursive feature elimination（SVM-RFE）,and their diagnostic efficacy was evaluated by ROC curve（AUC>0.8）.Finally, immune cell infiltration analysis was performed using CIBERSORT to verify the correlation between the core genes and immune cells.Results:A total of 1 187 PBMC-related DEGs were identified, including 447 upregulated and 740 downregulated genes.GO and KEGG analyses showed that upregulated DEGs were enriched in pathways such as myeloid cell activation and neutrophil extracellular trap formation; downregulated DEGs were enriched in T cell differentiation and coronavirus disease-related pathways.17 modules were identified by WGCNA,among which the pink module had the highest correlation with sepsis（r=0.82,P<0.001）.Through the combined Lasso regression model, RF, and SVM-RFE analysis, two core genes, FAM20A and C1QB,were finally selected, both of which were upregulated DEGs, and their AUC values were 0.969 and 0.957,respectively, showing significant diagnostic value.The immune infiltration analysis indicated that monocyte infiltration increased in the SEP group（P<0.05）,while CD8⁺T cells, resting CD4⁺T cells, and resting NK cells infiltration decreased（P<0.05）,and this was consistent with the infiltration situation of the core genes.Conclusion:PBMC participates in the progression of sepsis by regulating inflammation and immune imbalance.FAM20A and C1QB may be the key targets of PBMC in sepsis.更多还原