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采用 iTRAQ-2D-LC-MS/MS 技术进行血清蛋白质组分析鉴定脓毒症诊断的新型生物标志物。

Identification of novel biomarkers for sepsis diagnosis via serum proteomic analysis using iTRAQ-2D-LC-MS/MS.

机构信息

Department of Clinical Laboratory, Zhejiang Hospital, Hangzhou, China.

Department of Intensive Care, Zhejiang Hospital, Hangzhou, China.

出版信息

J Clin Lab Anal. 2022 Jan;36(1):e24142. doi: 10.1002/jcla.24142. Epub 2021 Nov 26.

DOI:10.1002/jcla.24142
PMID:34825737
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8761403/
Abstract

BACKGROUND

Sepsis is a common cause of morbidity and mortality in the ICU patients. Early diagnosis and appropriate patient management is the key to improve the patient survival and to limit disabilities in sepsis patients. This study was aimed to find new diagnostic biomarkers of sepsis.

METHODS

In this study, serum proteomic profiles in sepsis patients by iTRAQ2D-LC-MS/MS. Thirty seven differentially expressed proteins were identified in patients with sepsis, and six proteins including ApoC3, SERPINA1, VCAM1, B2M, GPX3, and ApoE were selected for further verification by ELISA and immunoturbidimetry in 53 patients of non-sepsis, 37 patients of sepsis, and 35 patients of septic shock. Descriptive statistics, functional enrichment analysis, and ROC curve analysis were conducted.

RESULTS

The level of ApoC3 was gradually decreased among non-sepsis, sepsis, and septic shock groups (p = 0.049). The levels of VCAM1 (p = 0.010), B2M (p = 0.004), and ApoE (p = 0.039) were showing an increased tread in three groups, with the peak values of B2M and ApoE in the sepsis group. ROC curve analysis for septic diagnosis showed that the areas under ROC curve (AUC) of ApoC3, VCAM1, B2M, and ApoE were 0.625, 0.679, 0.581, and 0.619, respectively, which were lower than that of PCT (AUC 0.717) and CRP (AUC 0.706), but there were no significant differences between each index and PCT or CRP. The combination including four validated indexes and two classical infection indexes for septic diagnosis had the highest AUC-ROC of 0.772.

CONCLUSION

Proteins of ApoC3, VCAM1, B2M, and ApoE provide a supplement to classical biomarkers for septic diagnosis.

摘要

背景

脓毒症是 ICU 患者发病率和死亡率的常见原因。早期诊断和适当的患者管理是提高患者生存率和限制脓毒症患者残疾的关键。本研究旨在寻找脓毒症的新诊断生物标志物。

方法

在这项研究中,通过 iTRAQ2D-LC-MS/MS 分析脓毒症患者的血清蛋白质组谱。在 37 例脓毒症患者中鉴定出 37 个差异表达蛋白,其中 6 个蛋白包括 ApoC3、SERPINA1、VCAM1、B2M、GPX3 和 ApoE,通过 ELISA 和免疫比浊法在 53 例非脓毒症患者、37 例脓毒症患者和 35 例脓毒性休克患者中进一步验证。进行描述性统计、功能富集分析和 ROC 曲线分析。

结果

非脓毒症、脓毒症和脓毒性休克组的 ApoC3 水平逐渐降低(p=0.049)。VCAM1(p=0.010)、B2M(p=0.004)和 ApoE(p=0.039)水平在三组中呈升高趋势,B2M 和 ApoE 的峰值在脓毒症组。脓毒症诊断的 ROC 曲线分析显示,ApoC3、VCAM1、B2M 和 ApoE 的 ROC 曲线下面积(AUC)分别为 0.625、0.679、0.581 和 0.619,低于 PCT(AUC 0.717)和 CRP(AUC 0.706),但各指标与 PCT 或 CRP 之间无显著差异。包括四个验证指标和两个经典感染指标的脓毒症诊断组合的 AUC-ROC 最高,为 0.772。

结论

ApoC3、VCAM1、B2M 和 ApoE 等蛋白为脓毒症诊断提供了经典生物标志物的补充。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7937/8761403/6fc97312c8a8/JCLA-36-e24142-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7937/8761403/7c1a2fd8a377/JCLA-36-e24142-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7937/8761403/6fc97312c8a8/JCLA-36-e24142-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7937/8761403/7c1a2fd8a377/JCLA-36-e24142-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7937/8761403/6fc97312c8a8/JCLA-36-e24142-g001.jpg

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