综合生物信息学分析阐明免疫血栓形成的分子特性与诊疗潜力  

Unveiling the molecular features and diagnosis and treatment prospects of immunothrombosis via integrated bioinformatics analysis

作　　者：王雅芬 吴晓双 刘志新 李欣蕾 陈要臻 安宁 胡兴斌 WANG Yafen;WU Xiaoshuang;LIU Zhixin;LI Xinlei;CHEN Yaozhen;AN Ning;HU Xingbin(Department of Blood Transfusion,The First Affiliated Hospital,Air Force Medical University,Xi’an 710032,China)

机构地区：[1]空军军医大学第一附属医院输血科,陕西西安710032

出　　处：《细胞与分子免疫学杂志》2025年第3期228-235,共8页Chinese Journal of Cellular and Molecular Immunology

基　　金：陕西省自然科学基础研究计划(2024JC-YBQN-0890)。

摘　　要：目的 本研究旨在探讨免疫血栓形成的共同分子特征,以期深入理解由免疫炎症反应所诱发的血栓形成过程,为发掘潜在的诊疗靶点提供重要依据。方法 对系统性红斑狼疮(SLE)和静脉血栓栓塞症(VTE)数据集进行差异表达基因鉴定和功能富集分析,随后与中性粒细胞外陷阱(NET)的差异表达基因取交集,得到SLE-NET和VTE-NET的串扰基因(CG)。对这些CG进行功能富集和蛋白质互作(PPI)网络分析,以识别中枢(hub)基因。使用维恩图和受试者工作特征(ROC)曲线分析筛选最佳共享诊断CG,并在移植物抗宿主病(GVHD)数据集中进行了验证。结果 SLE和VTE的差异表达基因分别富集于不同的生物学过程,而SLE-NET-CG和VTE-NET-CG则共同涉及白细胞迁移、炎症反应和免疫反应等途径。通过PPI网络分析,识别出多个hub基因,其中基质金属蛋白酶9(MMP9)和S100钙结合蛋白A12(S100A12)被鉴定为SLE[ROC曲线下的面积(AUC)分别为0.936和0.832]和VTE(AUC分别为0.719和0.759)的最佳共享诊断CG。在GVHD数据集中,也证实MMP9具有较好的诊断效能(AUC:0.696)。结论 本研究揭示了SLE、 VTE和NET的共同分子特征,筛选出MMP9和S100A12作为最佳共享诊断CG,为免疫血栓形成的诊疗策略提供了重要依据。同时,MMP9在GVHD中的表达验证了其在免疫系统疾病VTE风险中的关键作用。Objective To investigate the common molecular features of immunothrombosis,thus enhancing the comprehension of thrombosis triggered by immune and inflammatory responses and offering crucial insights for identifying potential diagnostic and therapeutic targets.Methods Differential gene expression analysis and functional enrichment analysis were conducted on datasets of systemic lupus erythematosus(SLE)and venous thromboembolism(VTE).The intersection of differentially expressed genes in SLE and VTE with those of neutrophil extracellular traps(NET)yielded cross-talk genes(CG)for SLE-NET and VTE-NET interaction.Further analysis included functional enrichment and protein-protein interaction(PPI)network assessments of these CG to identify hub genes.Venn diagrams and receiver operating characteristic(ROC)curve analysis were employed to pinpoint the most effective shared diagnostic CG,which were validated using a graft-versus-host disease(GVHD)dataset.Results Differential expression genes in SLE and VTE were associated with distinct biological processes,whereas SLE-NET-CG and VTE-NET-CG were implicated in pathways related to leukocyte migration,inflammatory response,and immune response.Through PPI network analysis,several hub genes were identified,with matrix metalloproteinase 9(MMP9)and S100 calcium-binding protein A12(S100A12)emerging as the best shared diagnostic CG for SLE(AUC:0.936 and 0.832)and VTE(AUC:0.719 and 0.759).Notably,MMP9 exhibited good diagnostic performance in the GVHD dataset(AUC:0.696).Conclusion This study unveils the common molecular features of SLE, VTE, and NET, emphasizing MMP9 and S100A12 as the optimal shared diagnostic CG, thus providing valuable evidence for the diagnosis and therapeutic strategies related to immunothrombosis. Additionally, the expression of MMP9 in GVHD highlights its critical role in the risk of VTE associated with immune system disorders.

关 键 词：免疫血栓形成 系统性红斑狼疮(SLE) 静脉血栓栓塞症(VTE) 中性粒细胞外陷阱(NET) 移植物抗宿主病(GVHD) 生物信息学分析 基质金属蛋白酶9(MMP9) 

分 类 号：R392[医药卫生—免疫学] R593.241[医药卫生—基础医学] R857.3