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通过蛋白质组学方法鉴定重症腺病毒社区获得性肺炎的候选生物标志物

Identification of candidate biomarkers for severe adenovirus community-acquired pneumonia by proteomic approach.

作者信息

Shi Tingting, Bai Jun, Yang Diyuan, Huang Li, Fan Hui-Feng, Zhang Dong-Wei, Liu Tongzheng, Lu Gen

机构信息

Department of Respiratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

Affiliated Foshan Maternity &Child Healthcare Hospital, Southern Medical University.

出版信息

Heliyon. 2022 Sep 28;8(10):e10807. doi: 10.1016/j.heliyon.2022.e10807. eCollection 2022 Oct.

Abstract

INTRODUCTION

Worldwide, Human adenoviruses (ADV) cause a significant portion of childhood mortality. The severity of ADV Community-acquired Pneumonia (CAP) can be assessed by clinical features, but the rapid and accurate diagnostic biomarkers are still lacking. Candidate biomarkers for severe ADV CAP are to be screened and the different protein expression levels associated with pediatric ADV CAP may help assess the severity of ADV CAP for the pediatricians to make early intervention.

METHODS

In our study, serum samples from healthy controls, patients with ADV CAP, streptococcus pneumonia (SP) and respiratory syncytial virus (RSV) infection were collected. Differently expressed proteins (DEPs) were detected by iTRAQ-based mass spectrometry. Gene Ontology and Pathway Enrichment analysis of DEPs were performed by Cytoscape. The protein interaction network for the identified proteins was constructed by String.

RESULTS

The results showed that 119 DEPs in mild ADV CAP and 148 DEPs in severe ADV CAP were identified, compared with healthy children. Four proteins (Protein S100-A9 (S100A9), Protein S100-A8 (S100A8), Leucine aminopeptidase III (LAP3), and Apolipoprotein A-IV(APOA4)) were validated by Western blot, and results indicated that the expression levels of these four proteins were consistent with the proteomic analysis. LAP3 was the most significantly up-regulated protein in severe ADV CAP compared to mild group. In addition, LAP3 was the most significantly up-regulated protein in severe ADV CAP comparing with SP CAP infection and RSV CAP infection.

CONCLUSION

Our findings identified LAP3 protein as a potential diagnostic biomarker which can assess the severity of ADV CAP.

摘要

引言

在全球范围内,人类腺病毒(ADV)导致了相当一部分儿童死亡。ADV社区获得性肺炎(CAP)的严重程度可通过临床特征进行评估,但仍缺乏快速准确的诊断生物标志物。需要筛选出重症ADV CAP的候选生物标志物,与儿童ADV CAP相关的不同蛋白质表达水平可能有助于评估ADV CAP的严重程度,以便儿科医生进行早期干预。

方法

在我们的研究中,收集了健康对照、ADV CAP患者、肺炎链球菌(SP)和呼吸道合胞病毒(RSV)感染患者的血清样本。通过基于iTRAQ的质谱法检测差异表达蛋白(DEP)。通过Cytoscape对DEP进行基因本体论和通路富集分析。利用String构建已鉴定蛋白质的蛋白质相互作用网络。

结果

结果显示,与健康儿童相比,轻度ADV CAP中有119个DEP,重度ADV CAP中有148个DEP。通过蛋白质印迹法验证了四种蛋白质(蛋白质S100 - A9(S100A9)、蛋白质S100 - A8(S100A8)、亮氨酸氨肽酶III(LAP3)和载脂蛋白A-IV(APOA4)),结果表明这四种蛋白质的表达水平与蛋白质组学分析一致。与轻度组相比,LAP3是重度ADV CAP中上调最显著的蛋白质。此外,与SP CAP感染和RSV CAP感染相比,LAP3是重度ADV CAP中上调最显著的蛋白质。

结论

我们的研究结果确定LAP3蛋白是一种潜在的诊断生物标志物,可用于评估ADV CAP的严重程度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/953f/9547224/445c821e7a3d/gr1.jpg

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