Sci Rep. 2026 Jan 26. doi: 10.1038/s41598-026-36494-2. Online ahead of print.
ABSTRACT
Identifying reliable circulating biomarkers is crucial for improving the diagnosis and risk stratification of patients with ischemic stroke. In this study, we evaluated several whole-blood circulating miRNAs (miR-106b-5p, miR-16-5p, miR-15b-5p, let-7e-5p, and miR-125a-3p/-5p) to determine their diagnostic and disease severity in acute ischemic stroke (AIS). Sixty AIS patients and thirty age- and sex-matched controls were included. Whole-blood miRNAs were quantified at admission and on day 7. Statistical analyses included ROC curves, multivariate logistic regression, and SHAP-based machine learning. Bioinformatic analyses assessed predicted miRNA targets, pathway enrichment, and interaction networks. MiR-125a-3p was significantly reduced in AIS at both time points, while miR-125a-5p was elevated at admission and decreased by day 7. Both miRNAs showed moderate diagnostic value (AUC 0.675 and 0.712, respectively). Higher admission levels of miR-16-5p were strongly associated with greater neurological deficit (NIHSS) and unfavorable outcome (mRS ≥ 3). Multivariate analyses confirmed high miR-16-5p and elevated CRP as independent predictors of poor outcome. Bioinformatic analyses revealed that miR-16-5p targets were enriched in pathways relevant to ischemic injury, including hypoxia response, platelet activation, coagulation, TGF-β and BDNF signaling. A target-interaction network highlighted IL6, FN1, TGFB1, ICAM1, and TLR4 as central nodes linking miR-16-5p to ischemia-inflammatory mechanisms in AIS. Circulating miRNAs display distinct expression patterns in the acute phase of AIS. miR-16-5p emerges as a promising biomarker associated with stroke severity and unfavorable outcome, while miR-125a-3p and miR-125a-5p show potential diagnostic utility. These findings strengthen mechanistic links between platelet-derived miRNAs and ischemic stroke biology. Larger, longitudinal studies integrating functional validation are warranted to confirm their clinical value.
PMID:41582192 | DOI:10.1038/s41598-026-36494-2
