基于DIA蛋白组学构建脓毒症性凝血病诊断模型的临床研究  

A clinical investigation of constructing a diagnostic model for sepsis-induced coagulopathy utilizing data-independent acquisition proteomics

作　　者：陈奇[1] 宋景春 万小雷 曾俊杰[1] 宋晓敏 钟林翠 何龙平 Chen Qi;Song Jingchun;Wan Xiaolei;Zeng Junjie;Song Xiaomin;Zhong Lincui;He Longping(Intensive Care Unit,the 908th Hospital of Chinese PLA Logistical Support Force,Changcheng Hospital Affliated to Nanchang University,Nanchang 330002,China)

机构地区：[1]解放军联勤保障部队第九〇八医院重症医学科/南昌大学附属长城医院重症医学科,南昌330002

出　　处：《中华血液学杂志》2025年第1期45-52,共8页Chinese Journal of Hematology

基　　金：国家重点研发计划(2022YFC2304600)。

摘　　要：目的采用数据非依赖型采集(DIA)蛋白质组学技术分析脓毒症性凝血病(SIC)的血浆蛋白表达,筛选典型生物标志物并构建诊断模型。方法前瞻性观察研究纳入重症医学科46例成年脓毒症患者,收集临床资料并按照SIC标准分为普通脓毒症组(26例)和SIC组(20例),采集血浆标本进行蛋白组学检测并进行生信物信息学分析,应用LASSO、随机森林筛选差异表达蛋白(DEP),根据筛选结果构建SIC诊断模型,并进行受试者工作特征(ROC)曲线分析。结果基线资料显示,SIC患者的凝血酶原时间较脓毒症组明显延长,血小板计数明显降低,D-二聚体、纤维蛋白降解产物、血乳酸、SOFA评分和APACHEⅡ评分较脓毒症组患者明显升高(P<0.05)。DIA蛋白组学共鉴定出2637个蛋白,以表达倍数>1.5倍且P<0.05为筛选标准,共筛选出240个DEP,包括81个上调DEP和159个下调DEP。亚细胞定位分析表明,DEP主要在细胞外和细胞核;GO注释显示,DEP在生物过程方面主要参与细胞生理、生物调节和应激反应过程;分子功能方面主要参与生物分子互作和催化作用;结构域注释显示DEP以免疫球蛋白V区为主,是特异识别和结合抗原的部分;KEGG富集分析显示,DEP主要富集在自然杀伤细胞介导的细胞毒性反应、糖基磷脂酰肌醇锚定蛋白合成通路、肿瘤坏死因子信号通路和NF-κB信号通路。对DEP进行LASSO回归和随机森林,筛选出血管生成素、凝集素家族成员10两个变量,且以此构建的SIC诊断模型的ROC曲线下面积为0.896,特异度为0.731,灵敏度为0.900。结论由血管生成素、凝集素家族成员10构建的诊断模型可准确诊断SIC。ObjectiveThis study used data-independent acquisition(DIA)proteomics to analyze plasma protein expression in sepsis-induced coagulopathy(SIC),identify key biomarkers,and develop a diagnostic model.MethodsThis prospective study included 46 adult sepsis patients from the intensive care unit.Patients were categorized into a general sepsis group(n=26)and an SIC group(n=20)based on established SIC criteria.Plasma samples underwent proteomic and bioinformatics analyses to identify differentially expressed protein(DEP)using LASSO regression and Random Forest.A diagnostic model was constructed and assessed via receiver operating characteristic(ROC)curve analysis.ResultsThe baseline data revealed that SIC patients exhibited longer prothrombin times,lower platelet counts,and higher D-dimer,fibrin degradation products,blood lactate,SOFA scores,and APACHEⅡscores compared with general sepsis patients(P<0.05).DIA proteomics identified 2637 proteins,with 240 DEP meeting the criteria(fold change>1.5,P<0.05),including 81 upregulated and 159 downregulated DEP.Subcellular localization analysis revealed that DEPs were predominantly extracellular and nuclear.Gene ontology(GO)annotation showed that DEP were mainly involved in cellular physiology,biological regulation,and stress response processes in biological processes.Domain annotation revealed a predominance of immunoglobulin V regions in DEP,which are crucial for antigen recognition and binding.KEGG enrichment analysis showed significant enrichment of DEP in pathways related to natural killer cell-mediated cytotoxicity,glycosylphosphatidylinositol anchor biosynthesis,tumor necrosis factor signaling,and NF-κB signaling.LASSO regression identified angiogenin and C-type lectin domain family 10 member A as key DEP.The SIC diagnostic nomogram showed an area under the curve of 0.896,with 0.731 specificity and 0.900 sensitivity.ConclusionThe nomogram incorporating angiogenin and C-type lectin domain family 10 member A provides an accurate tool for SIC diagnosis.

关 键 词：脓毒症性凝血病 蛋白组学 诊断模型 列线图 血管生成素 

分 类 号：R459.7[医药卫生—急诊医学] R55[医药卫生—治疗学]