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Extracellular microRNAs in blood differentiate between ischaemic and haemorrhagic stroke subtypes
M Yashar S Kalani1, Eric Alsop2, Bessie Meechoovet2
1Departments of Neurological Surgery and Neuroscience, University of Virginia School of Medicine, Charlottesville, VA, USA.
Abstract:
Rapid identification of patients suffering from cerebral ischaemia, while excluding intracerebral haemorrhage, can assist with patient triage and expand patient access to chemical and mechanical revascularization. We sought to identify blood-based, extracellular microRNAs 15 (ex-miRNAs) derived from extracellular vesicles associated with major stroke subtypes using clinical samples from subjects with spontaneous intraparenchymal haemorrhage (IPH), aneurysmal subarachnoid haemorrhage (SAH) and ischaemic stroke due to cerebral vessel occlusion. We collected blood from patients presenting with IPH (n = 19), SAH (n = 17) and ischaemic stroke (n = 21). We isolated extracellular vesicles from plasma, extracted RNA cargo, 20 sequenced the small RNAs and performed bioinformatic analyses to identify ex-miRNA biomarkers predictive of the stroke subtypes. Sixty-seven miRNAs were significantly variant across the stroke subtypes. A subset of exmiRNAs differed between haemorrhagic and ischaemic strokes, and LASSO analysis could distinguish SAH from the other subtypes with an accuracy of 0.972 ± 0.002. Further analyses predicted 25 miRNA classifiers that stratify IPH from ischaemic stroke with an accuracy of 0.811 ± 0.004 and distinguish haemorrhagic from ischaemic stroke with an accuracy of 0.813 ± 0.003. Blood-based, ex-miRNAs have predictive value, and could be capable of distinguishing between major stroke subtypes with refinement and validation. Such a biomarker could one day aid in the triage of patients to expand the pool eligible for effective treatment.
Insights
Blood-based extracellular microRNAs (ex-miRNAs) can distinguish between major stroke subtypes. This discovery may improve patient triage and treatment access for conditions like cerebral ischaemia.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Molecular Biology
Background:
- Cerebral ischaemia and haemorrhagic stroke require rapid, accurate diagnosis for effective treatment.
- Current diagnostic methods can be time-consuming, delaying critical interventions.
- Extracellular vesicles (EVs) carry microRNAs (miRNAs) that may serve as diagnostic biomarkers.
Purpose of the Study:
- To identify blood-based extracellular microRNAs (ex-miRNAs) that differentiate major stroke subtypes.
- To assess the diagnostic potential of ex-miRNAs for intraparenchymal haemorrhage (IPH), aneurysmal subarachnoid haemorrhage (SAH), and ischaemic stroke.
Main Methods:
- Collected plasma samples from patients with IPH (n=19), SAH (n=17), and ischaemic stroke (n=21).
- Isolated extracellular vesicles (EVs) from plasma, extracted RNA, and performed small RNA sequencing.
- Utilized bioinformatic analyses, including LASSO, to identify predictive ex-miRNA biomarkers.
Main Results:
- Identified 67 significantly variant miRNAs across stroke subtypes.
- A subset of ex-miRNAs differentiated haemorrhagic from ischaemic strokes.
- LASSO analysis distinguished SAH from other subtypes with 0.972 accuracy.
- Developed 25 miRNA classifiers to differentiate IPH from ischaemic stroke (0.811 accuracy) and haemorrhagic from ischaemic stroke (0.813 accuracy).
Conclusions:
- Blood-based ex-miRNAs show predictive value for distinguishing major stroke subtypes.
- These ex-miRNAs could form the basis of a novel blood test for stroke diagnosis.
- Further validation may enable improved patient triage and expanded access to revascularization therapies.
