Extracellular non-coding RNA are emerging biomarkers across diseases, as they may represent the functional state of the cells of origin, and have been robustly detected and associated with disease in many biofluids, but not yet at a large scale in cerebrospinal fluid (CSF). While there have been extracellular non-coding RNA (exmiRNA) identified in small associative studies involving the CSF and patients with neurologic conditions, much remains to be determined, including what constitutes healthy CSF. In this work, we aggregate 9 existing cohorts to define a super-series of 864 extracellular circulating microRNA (exmiRNA) samples in the CSF from patients with 16 neurologic diseases and healthy controls. Through this, we identify broad patterns of conserved expression of CSF exmiRNA in the healthy state and in neurologic diseases, and a set of robustly detectable miRNA that may be strong biomarker candidates for future studies. We show that the coexpression network of exmiRNA differs significantly between the malignant and non-malignant states, suggesting that widespread dysregulation of miRNA due to cancer can be detected in the CSF. The super series will serve as a resource for future research in CSF exncRNA biomarkers, and will continue to evolve as more data is generated in this burgeoning field.

中文翻译：

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脑脊液中的超系列细胞外miRNA揭示了与神经系统疾病相关的广泛模式

细胞外非编码RNA是跨疾病的新兴生物标志物，因为它们可能代表起源细胞的功能状态，并已在许多生物流体中得到了稳健的检测并与疾病相关，但在脑脊液（CSF）中尚未大规模。尽管在涉及CSF和神经系统疾病患者的小型关联研究中已鉴定出细胞外非编码RNA（exmiRNA），但仍有很多待确定，包括构成健康CSF的成分。在这项工作中，我们汇总了9个现有队列，以定义来自16种神经系统疾病和健康对照患者的CSF中864个细胞外循环微RNA（exmiRNA）样本的超系列。通过这种方法，我们确定了健康状态和神经系统疾病中CSF exmiRNA保守表达的广泛模式，以及一组可强有力检测的miRNA，这些miRNA可能是未来研究的强生物标志物候选物。我们表明，exmiRNA的共表达网络在恶性和非恶性状态之间存在显着差异，这表明在CSF中可以检测到由于癌症引起的miRNA广泛失调。超级系列将作为CSF exncRNA生物标记物未来研究的资源，并将随着这一新兴领域中产生的更多数据而继续发展。