蛋白质组学联合转录组学鉴定脓毒血症诱导肺损伤的差异表达基因的效能及独立样本验证  

Efficiency of proteomics combined with transcriptomics in identifying differentially expressed genes in sepsis-induced lung injury and independent sample validation

作　　者：严东星 袁晓梅[1] 王志霞 王金会 YAN Dongxing;YUAN Xiaomei;WANG Zhixia;WANG Jinhui(the First Ward in Department of Respiratory and Critical Care Medicine,,the First Affiliated Hospital of Xinxiang Medical University,Weihui,Henan,453100;the Second Ward in Department of Respiratory and Critical Care Medicine,,the First Affiliated Hospital of Xinxiang Medical University,Weihui,Henan,453100;the First Ward in Department of Integrated Traditional Chinese and Western Medicine,the First Affiliated Hospital of Xinxiang Medical University,Weihui,Henan,453100)

机构地区：[1]新乡医学院第一附属医院呼吸与危重症医学科一病区,河南卫辉453100 [2]新乡医学院第一附属医院呼吸与危重症医学科二病区,河南卫辉453100 [3]新乡医学院第一附属医院中西医结合科一病区,河南卫辉453100

出　　处：《实用临床医药杂志》2025年第6期1-6,12,共7页Journal of Clinical Medicine in Practice

基　　金：中医药传承与创新人才工程项目(210999904);2021年河南省医学科技攻关计划联合共建项目(LHGJ20210504)。

摘　　要：目的基于蛋白质组学联合转录组学结果探讨脓毒血症诱导肺损伤的生物学标志物。方法纳入70例脓毒血症患者及70例脓毒血症诱导肺损伤患者作为研究对象。将140例患者分为实验组和验证组。实验组包括10例脓毒血症及10例脓毒血症诱导肺损伤患者,采用蛋白质组学分析血浆中的差异表达蛋白,并进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)富集分析。从基因表达综合数据库(GEO)下载脓毒血症诱导肺损伤的数据集GSE10474,采用GEO2R在线数据库分析脓毒血症诱导肺损伤的差异转录组学数据。采用韦恩图在线分析蛋白质组学及转录组学中有关脓毒血症诱导肺损伤的共同差异基因。验证组包括60例脓毒血症(脓毒血症组)患者和60例脓毒血症诱导肺损伤(脓毒血症诱导肺损伤组)患者,采用酶联免疫吸附测试(ELISA)检测并比较脓毒血症组与脓毒血症诱导肺损伤组外周血中蛋白表达水平的差异。采用受试者工作特征(ROC)曲线分析差异蛋白表达水平鉴别脓毒血症及脓毒血症诱导肺损伤的临床价值。结果蛋白质组学结果证实脓毒血症患者及脓毒血症诱导肺损伤患者血浆中存在显著差异表达蛋白共239个;相较于脓毒血症患者,脓毒血症诱导肺损伤患者共存在96个显著上调的蛋白,143个显著下调的蛋白。差异表达蛋白GO富集分析结果包括细胞质、微管结合、三磷酸腺苷(ATP)结合、对病毒的防御反应、免疫反应,KEGG富集分析结果包括代谢途径、白细胞介素-17(IL-17)信号通路及磷脂酰肌醇-3-激酶-蛋白激酶B(PI3K-Akt)信号通路。在GSE10474数据集中,相较于脓毒血症患者,脓毒血症诱导肺损伤患者中显著上调的基因77个,显著下调的基因142个。韦恩图结果显示蛋白质组学和转录组学中共同差异表达基因共6个,依次为BTNL8、FCGR2B、TAK1、KCNC1、TREM1和SEC31A。相较于脓毒血症组,脓毒血症诱Objective To investigate biomarkers for sepsis-induced lung injury based on results of proteomics combined with transcriptomics analyses.Methods A total of 70 patients with sepsis and 70 patients with sepsis-induced lung injury were included as research objects.These patients were divided into experimental group and validation group.The experimental group included 10 patients with sepsis and 10 patients with sepsis-induced lung injury.Proteomics was used to analyze differentially expressed proteins in plasma,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. The dataset GSE10474 of sepsis-induced lung injurywas downloaded from the Gene Expression Omnibus (GEO), and GEO2R online database was used to analyze differential transcriptomics data for sepsis-induced lung injury. A Venn diagram was used online to analyze common differentially expressed genes related to sepsis-induced lung injury in proteomics and transcriptomics. The validation group included 60 patients with sepsis (sepsis group) and 60 patients with sepsis-induced lung injury (sepsis-induced lung injury group). Enzyme-linked immunosorbent assay (ELISA) was used to detect and compare the differences in protein expression level in peripheral blood between the sepsis group and the sepsis-induced lung injury group. Receiver operating characteristic (ROC) curve was used to analyze the clinical value of differential protein expression level in distinguishing sepsis and sepsis-induced lung injury. Results Proteomics results confirmed the presence of 239 significantly differentially expressed proteins in the plasma of patients with sepsis and sepsis-induced lung injury. Compared with patients with sepsis, there were 96 significantly upregulated proteins and 143 significantly downregulated proteins in patients with sepsis-induced lung injury. The results of GO enrichment analysis of differentially expressed proteins included cytoplasm, microtubule binding, adenosine triphosphate (ATP) binding, defense resp

关 键 词：脓毒血症 肺损伤 蛋白质组学 转录组学 标志物 敏感度 特异度 差异表达基因 鉴别效能 

分 类 号：R563[医药卫生—呼吸系统] R593[医药卫生—内科学] R319[医药卫生—临床医学]