Blood RNA Biomarker Signatures for Early Diagnosis and Prognosis in Ischemic and Hemorrhagic Stroke: The IBIS ‐ CT1 Study

OBJECTIVE: To evaluate the expression of nine blood RNA biomarkers in a clinical trial based on genes previously identified in an experimental monkey model of stroke for diagnosis feasibility and prognostication. METHODS: IBIS-CT1 was a prospective longitudinal study enrolling patients with ischemic stroke (IS) or intracerebral hemorrhage (ICH) within 6 h of onset, compared with healthy controls (HC). Blood samples were collected at < 6 h (early), 12 h, 24 h, 48 h, 7 days, and 3 months. Target RNAs were quantified using reverse-transcription PCR or digital droplet PCR. Clinical severity and disability were assessed by NIHSS at admission and the modified Rankin Scale (mRS) at 3 months. RESULTS: Twenty HC, 20 IS, and 20 ICH patients were included. Compared with HC, IS patients showed significant early upregulation of genes ADM, DUSP1, HMOX1, HSPA1B, LDLR, and PTGS2 (all p ≤ 0.0002) and downregulation of BAG3 (p < 0.0001). Similar patterns were observed in ICH, with higher expression levels than in IS. In IS, higher NIHSS scores correlated with early upregulation of ADM, DUSP1, HMOX1, PTGS2, and GOS2, while lower BAG3 expression associated with poorer 3-month outcomes. Combined gene expression discriminated stroke from controls with an AUC of 0.914 (95% CI, 0.84-0.98). INTERPRETATION: Distinct blood gene-expression signatures differentiate stroke from controls and predict functional outcome, supporting their potential as diagnostic and prognostic biomarkers.