Stańczak Marcin, Wyszomirski Adam, Słonimska Paulina, Kołodziej Barbara, Jabłoński Bartosz, Stanisławska-Sachadyn Anna, Karaszewski Bartosz
Department of Adult Neurology, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland.
Department of Adult Neurology, University Clinical Center, Gdańsk, Poland.
Front Neurol. 2024 Jun 12;15:1399345. doi: 10.3389/fneur.2024.1399345. eCollection 2024.
Hemorrhagic transformation (HT) in acute ischemic stroke is likely to occur in patients treated with intravenous thrombolysis (IVT) and may lead to neurological deterioration and symptomatic intracranial hemorrhage (sICH). Despite the complex inclusion and exclusion criteria for IVT and some useful tools to stratify HT risk, sICH still occurs in approximately 6% of patients because some of the risk factors for this complication remain unknown.
This study aimed to explore whether there are any differences in circulating microRNA (miRNA) profiles between patients who develop HT after thrombolysis and those who do not.
Using qPCR, we quantified the expression of 84 miRNAs in plasma samples collected prior to thrombolytic treatment from 10 individuals who eventually developed HT and 10 patients who did not. For miRNAs that were downregulated (fold change (FC) <0.67) or upregulated (FC >1.5) with < 0.10, we investigated the tissue specificity and performed KEGG pathway annotation using bioinformatics tools. Owing to the small patient sample size, instead of multivariate analysis with all major known HT risk factors, we matched the results with the admission NIHSS scores only.
We observed trends towards downregulation of miR-1-3p, miR-133a-3p, miR-133b and miR-376c-3p, and upregulation of miR-7-5p, miR-17-3p, and miR-296-5p. Previously, the upregulated miR-7-5p was found to be highly expressed in the brain, whereas miR-1, miR-133a-3p and miR-133b appeared to be specific to the muscles and myocardium.
miRNA profiles tend to differ between patients who develop HT and those who do not, suggesting that miRNA profiling, likely in association with other omics approaches, may increase the current power of tools predicting thrombolysis-associated sICH in acute ischemic stroke patients. This study represents a free hypothesis-approach pilot study as a continuation from our previous work. Herein, we showed that applying mathematical analyses to extract information from raw big data may result in the identification of new pathophysiological pathways and may complete standard design works.
急性缺血性卒中患者接受静脉溶栓治疗后可能会发生出血性转化（HT），这可能导致神经功能恶化和症状性颅内出血（sICH）。尽管静脉溶栓有复杂的纳入和排除标准以及一些用于分层HT风险的有用工具，但sICH仍发生在约6%的患者中，因为该并发症的一些危险因素仍然未知。
本研究旨在探讨溶栓后发生HT的患者与未发生HT的患者之间循环微小RNA（miRNA）谱是否存在差异。
我们使用定量聚合酶链反应（qPCR）对10例最终发生HT的个体和10例未发生HT的患者在溶栓治疗前采集的血浆样本中84种miRNA的表达进行了定量。对于下调（倍数变化（FC）<0.67）或上调（FC>1.5）且P<0.10的miRNA，我们研究了其组织特异性，并使用生物信息学工具进行KEGG通路注释。由于患者样本量小，我们没有对所有已知的主要HT危险因素进行多变量分析，而是仅将结果与入院时的美国国立卫生研究院卒中量表（NIHSS）评分进行匹配。
我们观察到miR-1-3p、miR-133a-3p、miR-133b和miR-376c-3p有下调趋势，miR-7-5p、miR-17-3p和miR-296-5p有上调趋势。此前发现上调的miR-7-5p在脑中高表达，而miR-1、miR-133a-3p和miR-133b似乎对肌肉和心肌具有特异性。
发生HT的患者与未发生HT的患者之间miRNA谱往往存在差异，这表明miRNA谱分析可能与其他组学方法相结合，可能会增强当前预测急性缺血性卒中患者溶栓相关sICH的工具的效能。本研究是一项自由假设方法的探索性研究，是我们之前工作的延续。在此，我们表明应用数学分析从原始大数据中提取信息可能会识别新的病理生理途径，并可能完成标准设计工作。
