活动性结核病血浆代谢性生物标志物筛选及诊断效能评价  

Screening and diagnostic efficacy evaluation of metabolomics biomarkers in patients with active tuberculosis

作　　者：周爱萍[1] 纪凌云 郭建[1] 倪丽君[1] 王东江 吕莉[1] 胡靓[1] 吴文娟[1] Zhou Aiping;Ji Lingyun;Guo Jian;Ni Lijun;Wang Dongjiang;Lyu Li;Hu Liang;Wu Wenjuan(Department of Laboratory Medicine,Shanghai East Hospital(South Division),School of Medicine,Tongji University,Shanghai 200123,China)

机构地区：[1]同济大学附属东方医院南院医学检验科,上海200123

出　　处：《中华检验医学杂志》2022年第3期275-281,共7页Chinese Journal of Laboratory Medicine

基　　金：上海市卫生计生委重点项目(201540028);上海市公共卫生体系建设三年行动计划(2020-2022年)(GWV-10.1-XK04)。

摘　　要：目的应用超高效液相色谱串联四级杆飞行时间质谱(UPLC-Q-TOF/MS)技术,筛选对结核病诊断有辅助意义的代谢性生物标志物。方法回顾性病例对照的临床研究。随机选取2017年1月至2018年1月就诊于上海市肺科医院和上海市东方医院的102例结核病患者[男49例,女53例,年龄为40.0(24.0,48.5)岁]、100例就诊于上海市东方医院经结核分枝杆菌γ干扰素释放试验(TB-IGRA)检测为阳性者[男55例,女45例,年龄为44.0(37.0,52.0)岁]和96名健康体检者[男55例,女41例,年龄为43.0(32.2,52.8)岁]。采用UPLC-Q-TOF/MS技术分别检测其血浆中的小分子代谢物,结合多元统计方法变量投影重要性(Variable Importance Projection,VIP)及单变量统计分析t检验方法筛选活动性结核病患者血浆中主要的差异代谢物,并对代谢差异物进行单变量受试者工作特性(ROC)曲线分析,计算曲线下面积值及用于结核病诊断的特异度和敏感度。结果所有样本检测得到10266个变量,经人类代谢组数据库检索定性,初步鉴定出1153种物质。3组样本两两比较后,将同时满足VIP>1和P<0.05的差异代谢物绘制韦恩图,得到的交集中含有38种主要差异代谢物。ROC曲线评估38个主要差异代谢物对活动性结核病的诊断效能,发现乳酸、多巴胺、9-十五碳烯酸及12,13-二羟基亚油酸在诊断活动性结核病时,其曲线下面积分别是0.92、0.98、0.94和0.94,特异度均大于90%,敏感度均大于80%,4种代谢标志物联合诊断活动性结核病的特异度和敏感度均为94%。结论筛选出的4种代谢标志物乳酸、多巴胺、9-十五碳烯酸及12,13-二羟基亚油酸对结核病的诊断具有良好的诊断效能。Objective Based on UPLC-Q-TOF/MS,to screen a panel of plasma metabolite biomarkers for TB diagnosis and evaluate its diagnostic efficacy.Methods 102 active TB patients[49 males,53 females,age 40.0(24.0,48.5)years]from Shanghai Pulmonary Hospital and Shanghai East Hospital from January 2017 to January 2018,100 TB-IGRA positive patients[55 males,45 females,age 44.0(37.0,52.0)years]and 96 healthy controls[55 males,41 females,age 43.0(32.2,52.8)years]from Shanghai East Hospital were randomly enrolled.UPLC-Q-TOF/MS technology was used to detect small molecule metabolites in plasma.Combined with multivariate statistical methods VIP and univariate statistic analysis Student's t-test,the main differential metabolites in the plasma of patients with active tuberculosis were filtered.The ROC curve was analyzed for the differential metabolites,and the AUC value,specificity,and sensitivity for diagnosis were used to screen metabolic biomarkers with diagnostic potential.Results All the samples examined resulted in 10266 variables,and 1153 substances were identified by qualitative retrieval through the human metabolome database.After pairwise comparison of samples from the three groups,differential metabolites that simultaneously satisfied VIP>1 and P<0.05 were plotted into a Venn diagram,and the resulting intersection set contained 38 major differential metabolites.The ROC curve analysis of 38 major metabolites showed that the area under the curve of lactic acid,dopamine,9-pentadecenoic acid,and 12,13-dihydroxy octadecadienoic acid in the diagnosis of active tuberculosis were 0.92,0.98,0.94,and 0.94,respectively,the specificity was both more than 90%and the sensitivity was both more than 80%.The specificity and sensitivity of four metabolites in the combined diagnosis of active tuberculosis were both 94%.Conclusion Lactic acid,dopamine,9-pentadecenoic acid,and 12,13-dihydroxy octadecadienoic acid can be used as potential metabolic biomarkers for tuberculosis diagnosis.

关 键 词：结核病 代谢组学 生物标志物 诊断效能评价 

分 类 号：R52[医药卫生—内科学]