Diagnostic performance of circulating microRNAs for the early diagnosis of different types of acute cerebrovascular disease

Early differentiation of acute cerebrovascular conditions is important for timely clinical management, while blood-based markers that could complement established diagnostic approaches remain under investigation. This exploratory case-control study evaluated the circulating expression and diagnostic performance of seven candidate microRNAs (miRNAs) in acute ischemic stroke (AIS), hemorrhagic stroke (HS), and transient ischemic attack (TIA) during the first 12 h after symptom onset. The study included 200 participants: 50 patients with AIS, 50 with HS, 50 with TIA, and 50 controls. Plasma was collected from the clinical groups at 3–4.5 h and 12 h after symptom onset and from controls at a single time point. Expression levels of let-7e-5p, miR-21-5p, miR-107, miR-125b-5p, miR-130a-3p, miR-143-3p, and miR-222-3p were measured using real-time quantitative polymerase chain reaction (RT-qPCR). Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis and binary logistic regression. let-7e-5p showed the most consistent expression pattern, with lower levels in AIS, HS, and TIA than in controls at both sampling time points. miR-107 was lower in AIS and HS than in controls at both time points, whereas miR-125b-5p showed a predominantly AIS-related pattern. Among comparisons with controls, let-7e-5p yielded the highest individual area under the ROC curve (AUC), reaching 0.867 for AIS at 12 h, whereas miR-222-3p yielded the highest individual AUC for AIS versus HS (0.833 at 12 h). Multi-miRNA models did not significantly improve discrimination over the best-performing individual markers. In the complete-case subset, adding let-7e-5p to a model comprising routinely available clinical variables was associated with a higher AUC for AIS versus controls (0.982) than either component alone. Overall, the observed expression and discrimination patterns support further investigation of circulating miRNAs as complementary markers in acute cerebrovascular disease. Prospective evaluation in larger, independent cohorts, including patients with stroke-mimicking conditions, is needed to determine their diagnostic performance and incremental value in real-world clinical settings.