目的:器官功能障碍的早期诊断和预测对于干预和改善脓毒症患者的预后至关重要。该研究旨在为围手术期脓毒症患者寻找新的器官功能障碍诊断和预测生物标志物。
方法:这是一个前瞻性的,控制,初步,和急诊手术患者的单中心研究。质谱,基因本体论(GO)功能分析,并进行蛋白质-蛋白质相互作用(PPI)网络以鉴定脓毒症患者的差异表达蛋白(DEP),通过酶联免疫吸附测定(ELISA)进行进一步验证。Logistic回归分析用于估计所选择的脓毒症患者的血清蛋白水平与临床预后的相对相关性。绘制校准曲线以评估模型的校准。
结果:通过质谱分析每组5份随机血清样本,并确定了146个DEP。进行GO功能分析和PPI网络以评估DEP的分子机制。选择六个DEP用于通过ELISA进一步验证。组织蛋白酶B(CatB),血管细胞粘附蛋白1(VCAM-1),中性粒细胞明胶酶相关脂质运载蛋白(NGAL),蛋白S100-A9,prosaposin,与对照组相比,脓毒症患者的血小板反应蛋白-1水平显着升高(p<0.001)。Logistic回归分析显示,CatB,S100-A9,VCAM-1,prosaposin,NGAL可用于器官功能障碍的术前诊断和术后预测。CatB和S100-A9是脓毒症患者术前诊断肾功能衰竭的可能预测因素。使用自举验证评估内部验证。肾功能衰竭模型的术前诊断显示出良好的区分性,C指数为0.898(95%置信区间0.843-0.954),校准良好。
结论:血清CatB,S100-A9,VCAM-1,prosaposin,NGAL可能是器官功能障碍的术前诊断和术后预测的新标志物。具体来说,S100-A9和CatB是脓毒症患者术前肾功能不全的指标。结合这两种生物标志物可以提高预测术前脓毒症肾功能不全的准确性。
背景:该研究于2022年6月1日在中国临床试验注册中心(ChiCTR2200060418)注册。
OBJECTIVE: Early diagnosis and prediction of organ dysfunction are critical for intervening and improving the outcomes of septic patients. The study aimed to find novel diagnostic and predictive biomarkers of organ dysfunction for perioperative septic patients.
METHODS: This is a prospective, controlled, preliminary, and single-center study of emergency surgery patients. Mass spectrometry, Gene Ontology (GO) functional analysis, and the protein-protein interaction (PPI) network were performed to identify the differentially expressed proteins (DEPs) from sepsis patients, which were selected for further verification via enzyme-linked immunosorbent assay (ELISA). Logistic regression analysis was used to estimate the relative correlation of selected serum protein levels and clinical outcomes of septic patients. Calibration curves were plotted to assess the calibration of the models.
RESULTS: Five randomized serum samples per group were analyzed via mass spectrometry, and 146 DEPs were identified. GO functional analysis and the PPI network were performed to evaluate the molecular mechanisms of the DEPs. Six DEPs were selected for further verification via ELISA. Cathepsin B (CatB), vascular cell adhesion protein 1 (VCAM-1), neutrophil gelatinase-associated lipocalin (NGAL), protein S100-A9, prosaposin, and thrombospondin-1 levels were significantly increased in the patients with sepsis compared with those of the controls (p < 0.001). Logistic regression analysis showed that CatB, S100-A9, VCAM-1, prosaposin, and NGAL could be used for preoperative diagnosis and postoperative prediction of organ dysfunction. CatB and S100-A9 were possible predictive factors for preoperative diagnosis of renal failure in septic patients. Internal validation was assessed using the bootstrapping validation. The preoperative diagnosis of renal failure model displayed good discrimination with a C-index of 0.898 (95% confidence interval 0.843-0.954) and good calibration.
CONCLUSIONS: Serum CatB, S100-A9, VCAM-1, prosaposin, and NGAL may be novel markers for preoperative diagnosis and postoperative prediction of organ dysfunction. Specifically, S100-A9 and CatB were indicators of preoperative renal dysfunction in septic patients. Combining these two biomarkers may improve the accuracy of predicting preoperative septic renal dysfunction.
BACKGROUND: The study was registered at the Chinese Clinical Trials Registry (ChiCTR2200060418) on June 1, 2022.