基于蛋白组学筛选的外周血蛋白在脓毒症诊断中的应用

Application of peripheral blood protein in the diagnosis of sepsis based on proteomics screening

目的研究前期基于蛋白组学筛选的外周血蛋白人可溶性髓系细胞触发受体-1(sTREM-1)、高迁移率族蛋白B1(HMGB-1)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、基质金属蛋白酶-8(MMP-8)在脓毒症诊断中的价值。方法选取2020年12月—2021年12月上海市第五人民医院中心监护室收治的60例脓毒症患者为脓毒症组,同时选取60例同期住院的非脓毒症感染患者为对照组。入组时检测2组患者血清中HMGB-1、NGAL、MMP-8、sTREM-1的表达水平。对纳入的变量进行共线性分析,排除方差膨胀因子>10的变量。共线性诊断后进行单因素和多因素Logistic回归分析。采用受试者工作特征(ROC)曲线对脓毒症进行诊断分析。采用Spearman分析HMGB-1、NGAL、MMP-8、sTREM-1与急性生理与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分、序贯器官衰竭估计量表(SOFA)评分、降钙素原(PCT)、C反应蛋白(CRP)的相关性。结果脓毒症组HMGB-1、NGAL、MMP-8、sTREM-1的表达水平高于对照组,差异有统计学意义(P<0.05)。共线性分析表明,HMGB-1、NGAL、MMP-8与sTREM-1共线性较低。采用单因素和多因素Logistic回归分析结果发现,NGAL和MMP-8是脓毒症的独立预测因子。NGAL、MMP-8、白细胞计数、PCT的ROC曲线的曲线下面积(AUC)分别为0.95(95%CI:0.91~0.99)、0.80(95%CI:0.71~0.89)、0.89(95%CI:1.00~1.09)和0.96(95%CI:1.07~1.17)。血浆sTREM-1、NGAL、HMGB-1、MMP-8均分别与CRP、PCT、SOFA评分、APACHEⅡ评分呈显著正相关(P<0.01)。结论脓毒症患者sTREM-1、NGAL、HMGB-1和MMP-8水平较高。NGAL和MMP-8是脓毒症的独立预测因子。

Objective To explore the value of peripheral blood protein including soluble triggering receptor expressed on myeloid cells-1(sTREM-1),high mobility group box-1(HMGB-1),neutrophil gelatinase-associated lipocalin(NGAL),and matrix metalloproteinase-8(MMP-8)screened by proteomics in the diagnosis of sepsis.Methods Sixty patients with sepsis admitted to the Central Care Unit of Shanghai Fifth People′s Hospital from December 2020 to December 2021 were selected as sepsis group,and 60 patients with non-sepsis infection admitted during the same period were selected as control group.The expression levels of HMGB-1,NGAL,MMP-8,and sTREM-1 in the serum of both patient groups were measured on admission.Variables were subjected to collinearity analysis,and variables with a variance inflation factor(VIF)>10 were excluded.Univariateand multivariate Logistic regression analyses were performed following collinearity diagnosis.Receiver operating characteristic(ROC)curve was used to diagnose sepsis.Correlations of HMGB-1,NGAL,MMP-8,sTREM-1 with Acute Physiology and Chronic Health EvaluationⅡ(APACHEⅡ)score,Sequential Organ Failure Assessment(SOFA)score,procalcitonin(PCT),and C-reactive protein were analyzed using Spearman analysis.Results The expression levels of HMGB-1,NGAL,MMP-8,and sTREM-1 in the sepsis group were significantly higher than those in the control group(P<0.05).Collinearity analysis showed that HMGB-1,NGAL,MMP-8,and sTREM-1 had low collinearity.Univariate and multivariate Logistic regression analyses revealed that NGAL and MMP-8 were independent predictors of sepsis.The area under the curve(AUC)for NGAL,MMP-8,white blood cells count,and PCT were 0.95(95%CI,0.91 to 0.99),0.80(95%CI,0.71 to 0.89),0.89(95%CI,1.00 to 1.09)and 0.96(95%CI,1.07 to 1.17),respectively.Plasma sTREM-1,NGAL,HMGB-1,and MMP-8 were all respectively positively correlated with CRP,PCT,SOFA score,and APACHEⅡscore(P<0.01).Conclusion The levels of sTREM-1,NGAL,HMGB-1,and MMP-8 are higher in the sepsis patients.In addition,NGAL and MMP-8 are independent predictors of sepsis.