Background

Detection of brain-specific miRNAs in the peripheral blood could serve as a surrogate marker of traumatic brain injury (TBI). Here, we systematically identified brain-enriched miRNAs, and tested their utility as TBI biomarkers in the acute phase of care.

Methods

Publically available microarray data generated from 29 postmortem human tissues were used to rank 1,364 miRNAs in terms of their degree of brain-specific expression. Levels of the top six ranked miRNAs were then prospectively measured in serum samples collected from 10 Patients with TBI at hospital admission, as well as from 10 controls.

Results

The top six miRNAs identified in our analysis (miR-124-3p, miR-219a-5p, miR-9-5p, miR-9-3p, miR-137, and miR-128-3p) were enriched 70 to 320-fold in brain relative to other tissues, and exhibited dramatically greater brain specificity compared to several miRNAs previously proposed as biomarkers. Furthermore, their levels were elevated in serum from patients with TBI compared to controls, and could collectively discriminate between groups with 90% sensitivity and 100% specificity. Interestingly, subsequent informatic pathway analysis revealed that their target transcripts were enriched for components of signaling pathways active in peripheral organs involved in common post-TBI complications.

Conclusions

The six candidate miRNAs identified in this preliminary study have promise as blood biomarkers of TBI, and could also be molecular contributors to systemic physiologic changes commonly observed post-injury.

中文翻译：

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脑特异性 miRNA 的生物信息学分析，用于鉴定候选的创伤性脑损伤血液生物标志物。

背景

外周血中脑特异性 miRNA 的检测可作为创伤性脑损伤 (TBI) 的替代标志物。在这里，我们系统地鉴定了富含大脑的 miRNA，并测试了它们在急性期护理中作为 TBI 生物标志物的效用。

方法

从 29 个死后人体组织产生的公开可用的微阵列数据被用于根据脑特异性表达程度对 1,364 个 miRNA 进行排名。然后在从入院时的 10 名 TBI 患者以及 10 名对照者收集的血清样本中前瞻性地测量排名前六位的 miRNA 的水平。

结果

我们分析中鉴定的前六种 miRNA（miR-124-3p、miR-219a-5p、miR-9-5p、miR-9-3p、miR-137 和 miR-128-3p）富集了 70 到 320-相对于其他组织在大脑中折叠，并且与之前提出作为生物标志物的几种 miRNA 相比，表现出显着更高的大脑特异性。此外，与对照组相比，TBI 患者的血清中它们的水平升高，并且可以以 90% 的敏感性和 100% 的特异性共同区分各组。有趣的是，随后的信息通路分析显示，它们的目标转录本富含在外周器官中活跃的信号通路成分，这些成分与常见的 TBI 后并发症有关。

结论

在这项初步研究中确定的六种候选 miRNA 有望作为 TBI 的血液生物标志物，也可能是损伤后常见的全身生理变化的分子贡献者。