Past studies suggest that there are changes in peripheral blood cell gene expression in response to ischaemic stroke; however, the specific changes which occur during the acute phase are poorly characterised. The current study aimed to identify peripheral blood cell genes specifically associated with the early response to ischaemic stroke using whole blood samples collected from participants diagnosed with ischaemic stroke (n = 29) or stroke mimics (n = 27) following emergency presentation to hospital. Long non-coding RNA (lncRNA), mRNA and micro-RNA (miRNA) abundance was measured by RNA-seq, and the consensusDE package was used to identify genes which were differentially expressed between groups. A sensitivity analysis excluding two participants with metastatic disease was also conducted. The mean time from symptom onset to blood collection was 2.6 h. Most strokes were mild (median NIH stroke scale score 2.0). Ten mRNAs (all down-regulated in samples provided by patients experiencing ischaemic stroke) and 30 miRNAs (14 over-expressed and 16 under-expressed in participants with ischaemic stroke) were significantly different between groups in the whole cohort and sensitivity analyses. No significant over-representation of gene ontology categories by the differentially expressed genes was observed. Random forest analysis suggested a panel of differentially expressed genes (ADGRG7 and miRNAs 96, 532, 6766, 6798 and 6804) as potential ischaemic stroke biomarkers, although modelling analyses demonstrated that these genes had poor diagnostic performance. This study provides evidence suggesting that the early response to minor ischaemic stroke is predominantly reflected by changes in the expression of miRNAs in peripheral blood cells. Further work in independent cohorts particularly in patients with more severe stroke is needed to validate these findings and investigate their clinical relevance.

中文翻译：

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诊断为轻度缺血性中风或类似中风的参与者急性期外周血基因表达的病例对照比较

过去的研究表明，缺血性中风导致外周血细胞基因表达发生变化。然而，急性期发生的具体变化尚不清楚。目前的研究旨在使用从被诊断为缺血性中风（n = 29）或中风模拟（n = 27）的参与者在紧急就诊后收集的全血样本来识别与缺血性中风早期反应特别相关的外周血细胞基因。通过RNA-seq测量长非编码RNA（lncRNA）、mRNA和微小RNA（miRNA）丰度，并使用consensusDE包识别组间差异表达的基因。还进行了排除两名患有转移性疾病的参与者的敏感性分析。从症状出现到采血的平均时间为 2.6 小时。大多数中风都是轻度的（NIH 中风量表评分中位数为 2.0）。在整个队列和敏感性分析中，10 种 mRNA（在缺血性中风患者提供的样本中全部下调）和 30 种 miRNA（缺血性中风参与者中 14 种过度表达和 16 种低表达）在各组之间存在显着差异。没有观察到差异表达基因对基因本体类别的显着过度表征。随机森林分析表明一组差异表达基因（ADGRG7 和 miRNA 96、532、6766、6798 和 6804）作为潜在的缺血性中风生物标志物，尽管模型分析表明这些基因的诊断性能较差。这项研究提供的证据表明，对轻微缺血性卒中的早期反应主要反映在外周血细胞中 miRNA 表达的变化。需要在独立队列中进行进一步的研究，特别是在患有更严重中风的患者中，以验证这些发现并调查其临床相关性。