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投稿时间：2025-12-23 网络发布日期：2026-05-22
投稿时间：2025-12-23 网络发布日期：2026-05-22
中文摘要: 目的 通过识别免疫调节相关差异表达基因（IRDEGs），为理解脓毒症诱导的急性呼吸窘迫综合征（ARDS）与免疫失衡相关的疾病机制及实现精准诊疗提供科学依据。方法 基于基因表达综合数据库（GEO）中的单纯脓毒症及脓毒症诱导的ARDS样本，筛选IRDEGs并进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。通过加权基因共表达网络分析（WGCNA）获得共表达模块基因，结合 logistic 回归、随机森林和LASSO回归构建ARDS诊断模型。同时，利用CIBERSORT进行免疫浸润分析，并收集2024年就诊于哈尔滨医科大学附属第一医院的脓毒症诱导的 ARDS 与单纯脓毒症患者的外周血样本各 10 例，通过酶联免疫吸附试验（ELISA）验证模型基因的蛋白表达。结果 鉴定出34个IRDEGs和4个模型基因［肿瘤坏死因子配体超家族成员10（TNFSF10）、β2-微球蛋白（B2M）、信号素7A（SEMA7A）和分化簇200（CD200）］，并构建了有效的ARDS诊断模型。免疫浸润显示ARDS中免疫细胞广泛富集且相关性显著，如滤泡辅助T细胞与静息树突状细胞呈强正相关（r=0.765，P＜0.05）。模型基因与免疫细胞浸润相关，如B2M与初始B细胞呈负相关（r=-0.383，P＜0.05）。ELISA证实，与单纯脓毒症患者相比，脓毒症诱导的 ARDS 患者血清中 CD200 和 SEMA7A 水平显著升高（P＜0.01）。结论 由TNFSF10、B2M、SEMA7A、CD200构建的ARDS诊断模型效能良好，模型基因和免疫细胞间以及各免疫细胞之间具有显著相关性，ELISA证实脓毒症ARDS患者血清CD200和SEMA7A显著升高，提示其为潜在诊断标志物。
Abstract:Objective To provide a scientific basis for understanding the disease mechanism and achieving precise diagnosis and treatment of sepsis-induced acute respiratory distress syndrome（ARDS）related to immune imbalance by identifying immune regulation-related differentially expressed genes（IRDEGs）. Methods Based on sepsis alone and sepsis-induced ARDS samples gained from the Gene Expression Omnibus（GEO）database，IRDEGs were screened and subjected to Gene Ontology（GO）and Kyoto Encyclopedia of Genes and Genomes（KEGG）pathway enrichment analyses. Weighted gene co-expression network analysis（WGCNA）was used to obtain co-expression module genes.Combined with logistic regression，random forest，and LASSO regression，an ARDS diagnostic model was constructed.Meanwhile，CIBERSORT was employed to analyze immune infiltration. Peripheral blood samples from patients with sepsis-induced ARDS and sepsis alone（n=10，each），treated at the First Affiliated Hospital of Harbin Medical University in 2024，were collected to validate the protein expression of model genes via enzyme-linked immunosorbent assay（ELISA）. Results A total of 34 IRDEGs and 4 model genes［tumor necrosis factor superfamily member 10（TNFSF10），β2-microglobulin（B2M），semaphorin 7A（SEMA7A），and cluster of differentiation 200（CD200）］were identified. An effective diagnostic model for ARDS was subsequently constructed. Immune infiltration analysis revealed extensive enrichment of immune cells and significant correlations in ARDS，such as a strong positive correlation between follicular helper T cells and resting dendritic cells（r=0.765，P＜0.05）. Model genes were associated with immune cell infiltration; for example，B2M was negatively correlated with naive B cells（r=-0.383，P＜0.05）. ELISA confirmed that serum levels of CD200 and SEMA7A were significantly higher in patients with sepsis-induced ARDS compared to those with sepsis alone（P＜0.01）. Conclusion The ARDS diagnostic model constructed using TNFSF10，B2M，SEMA7A，and CD200 exhibit good performance. There are significant correlations between the model genes and immune cells，as well as among various immune cells themselves. ELISA confirms that serum levels of CD200 and SEMA7A are significantly elevated in patients with septic ARDS，suggesting that they are potential diagnostic biomarkers.
文章编号： 中图分类号：R631 R563.8 文献标志码：A
基金项目:黑龙江省重点研发计划（GA21C011，JD22C005）
附件
引用文本：
熊雅欣,毛禹祁,谷全宽,等.脓毒症诱导的急性呼吸窘迫综合征免疫相关生物标志物的鉴定和验证[J].中国临床研究,2026,39(5):669-676.
熊雅欣,毛禹祁,谷全宽,等.脓毒症诱导的急性呼吸窘迫综合征免疫相关生物标志物的鉴定和验证[J].中国临床研究,2026,39(5):669-676.