Identification of Novel Circulating miRNAs in Patients with Acute Ischemic Stroke

Abstract

Ischemic strokes are associated with significant morbidity and mortality, but currently there are no reliable prognostic or diagnostic blood biomarkers. MicroRNAs (miRNAs) regulate various molecular pathways and may be used as biomarkers. Using RNA-Seq, we conducted comprehensive circulating miRNA profiling in patients with ischemic stroke compared with healthy controls. Samples were collected within 24 h of clinical diagnosis. Stringent analysis criteria of discovery (46 cases and 95 controls) and validation (47 cases and 96 controls) cohorts led to the identification of 10 differentially regulated miRNAs, including 5 novel miRNAs, with potential diagnostic significance. Hsa-miR-451a was the most significantly upregulated miRNA (FC; 4.8, FDR; 3.78 × 10−85), while downregulated miRNAs included hsa-miR-574-5p and hsa-miR-142-3p, among others. Importantly, we computed a multivariate classifier based on the identified miRNA panel to differentiate between ischemic stroke patients and healthy controls, which showed remarkably high sensitivity (0.94) and specificity (0.99). The area under the ROC curve was 0.97 and it is superior to other current available biomarkers. Moreover, in samples collected one month following stroke, we found sustained upregulation of hsa-miR-451a and downregulation of another 5 miRNAs. Lastly, we report 3 miRNAs that were significantly associated with poor clinical outcomes of stroke, as defined by the modified Rankin scores. The clinical translation of the identified miRNA panel may be explored further.

Efficacy of Rosuvastatin Combined with rt-PA Intravenous Thrombolytic Therapy for Elderly Acute Ischemic Stroke Patients

“…Stroke is a fatal disease that accounts for 5% of disability and 10% of deaths worldwide [ 1 , 2 ], of which approximately 80% are ischemic strokes [ 3 , 4 ]. Acute ischemic stroke (AIS) is most prevalent, which can lead to disability due to adverse events such as ischemic injury and neuronal cell death [ 5 ].…”

MicroRNA cerebrospinal fluid profile during the early brain injury period as a biomarker in subarachnoid hemorrhage patients

“…we found hsa-miR-320e and hsa-miR-451a that had already been described as potential biomarkers for early diagnosis of acute stroke (Stylli et al, 2017;Koopaei et al, 2021;Aldous et al, 2022) and hsa-miR-630 that had also been related with cancer disease (Wu et al, 2018;Liu et al, 2021) and SAH (Wang et al, 2014;Sun et al, 2019). Therefore, after an acute brain injury such as SAH, there seems to be an increased expression of specific miRNAs which might activate or inhibit signaling pathways responsible of DCI and clinical outcomes.…”

Identification of distinct circulating microRNAs in acute ischemic stroke patients with type 2 diabetes mellitus

“…RNA-Seq was performed on collected samples as previously described ( 41 ). Briefly, circulating miRNA from serum samples (200 μl) were extracted using miRNeasy Serum/Plasma Advanced Kit (Qiagen, Hilden, Germany) and RNA concentrations were measured by Qubit RNA Broad Range Assay Kit (Invitrogen, CA, USA).…”

“…We used a rigorous analysis approach for the robust identification of differentially expressed miRNAs. Using a similar approach, we have recently reported a panel of 10 differentially regulated miRNAs with remarkably high discriminatory performance between acute ischemic stroke patients and healthy controls ( 41 ). In the present study we focused our investigations on T2DM, a critical factor associated with stroke outcomes.…”