Circulating miR-151a-3p Is Associated with Cardioembolic Stroke Etiology: Pilot Study

Background
Reliable blood-based biomarkers for ischemic stroke, particularly for distinguishing stroke etiology, are currently lacking. Identification of cardioembolic stroke often requires prolonged cardiac monitoring, delaying etiological classification and secondary prevention. MicroRNAs (miRNAs) have emerged as promising biomarkers due to their stability in blood and disease-specific expression profiles.

Methods
We conducted a two-stage pilot study to identify circulating miRNAs associated with ischemic stroke etiology. In the discovery phase, expression of 352 miRNAs was screened in whole blood samples from 28 patients with acute ischemic stroke and 8 non-stroke neurological controls using multiplex RT-qPCR. In the validation phase, promising miRNAs were measured in an independent cohort of 69 ischemic stroke patients using two-tailed RT-qPCR assays, with a focus on discriminating cardioembolic from atherothrombotic stroke.

Results
In the screening phase, comparison of stroke etiologies identified nine miRNAs (hsa-miR-151a-3p, hsa-miR-23a-3p, hsa-miR-342-5p, hsa-miR-374a-5p, hsa-miR-374b-5p, hsa-miR-106b-3p, hsa-miR-22-3p, hsa-miR-625-5p, hsa-miR-361-5p) upregulated in cardioembolic stroke. In the validation cohort, only miR-151a-3p remained significantly upregulated in cardioembolic compared with atherothrombotic stroke (fold change 1.55, p = 0.03). Receiver operating characteristic analysis yielded an area under the curve of 0.67 (95% CI 0.53–0.82), with a sensitivity of 72% and specificity of 70%.

Conclusions
This two-stage study identifies miR-151a-3p as a potential blood-based biomarker of cardioembolic stroke etiology. Larger prospective studies will have to confirm its clinical utility and robustness in practice.