BACKGROUND A prompt diagnosis of HIE remains a challenge clinically. This study aimed to identify potential biomarkers of neonatal hypoxic-ischemic encephalopathy (HIE) via a novel proteomic approach, the isobaric tags for absolute and relative quantification (iTRAQ) method. METHODS Blood samples were collected from neonates with mild (n = 4), moderate (n = 4), or severe (n = 4) HIE who were admitted to the neonatal intensive care unit of Children's Hospital of Soochow University between Oct 2015 and Oct 2017. iTRAQ was performed in HIE patients and healthy controls (n = 4). Bioinformatics analyses including Gene Ontology and KEGG pathway enrichment analysis were performed to evaluate the potential features and capabilities of the identified differentially expressed proteins. RESULTS A total of 51 commonly differentially expressed proteins were identified among the comparisons between mild, moderate, and severe HIE as well as healthy controls. Haptoglobin (HP) and S100A8 were most significantly up-regulated in patients with HIE and further validated via real-time PCR and western blotting. The differentially expressed proteins represented multiple biological processes, cellular components and molecular functions and were markedly enriched in complement and coagulation cascades. CONCLUSIONS HP and S100A8 may serve as a potential biomarker for neonatal HIE and reflects the severity of HIE. The complement and coagulation cascades play crucial roles in the development of neonatal HIE.

中文翻译：

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使用iTRAQ鉴定新生儿缺氧缺血性脑病的新型生物标志物。

背景技术快速诊断HIE在临床上仍然是挑战。这项研究旨在通过一种新型的蛋白质组学方法，即用于绝对定量和相对定量的等压标记（iTRAQ）方法，来鉴定新生儿缺氧缺血性脑病（HIE）的潜在生物标志物。方法收集2015年10月至2015年10月间进入苏州大学儿童医院新生儿重症监护室的轻度（n = 4），中度（n = 4）或重度（n = 4）HIE新生儿的血液样本。 2017年。在HIE患者和健康对照组（n = 4）中进行了iTRAQ。进行了包括基因本体论和KEGG途径富集分析在内的生物信息学分析，以评估鉴定出的差异表达蛋白的潜在特征和能力。结果在轻度，中度和重度HIE以及健康对照之间的比较中，共鉴定出51种共同差异表达的蛋白质。HIE患者的肝炎球蛋白（HP）和S100A8最明显上调，并通过实时PCR和Western印迹进一步验证。差异表达的蛋白质代表多种生物学过程，细胞成分和分子功能，并且在补体和凝血级联反应中明显富集。结论HP和S100A8可作为新生儿HIE的潜在生物标志物，并反映HIE的严重程度。补体和凝血级联在新生儿HIE的发展中起关键作用。HIE患者中的肝红蛋白（HP）和S100A8显着上调，并通过实时PCR和Western印迹进一步验证。差异表达的蛋白质代表多种生物学过程，细胞成分和分子功能，并且在补体和凝血级联反应中明显富集。结论HP和S100A8可作为新生儿HIE的潜在生物标志物，并反映HIE的严重程度。补体和凝血级联在新生儿HIE的发展中起关键作用。HIE患者的肝炎球蛋白（HP）和S100A8最明显上调，并通过实时PCR和Western印迹进一步验证。差异表达的蛋白质代表多种生物学过程，细胞成分和分子功能，并且在补体和凝血级联反应中明显富集。结论HP和S100A8可作为新生儿HIE的潜在生物标志物，并反映HIE的严重程度。补体和凝血级联在新生儿HIE的发展中起关键作用。结论HP和S100A8可作为新生儿HIE的潜在生物标志物，并反映HIE的严重程度。补体和凝血级联在新生儿HIE的发展中起关键作用。结论HP和S100A8可作为新生儿HIE的潜在生物标志物，并反映HIE的严重程度。补体和凝血级联在新生儿HIE的发展中起关键作用。