Thrombus Metabolism‐Based Molecular Subtyping for Prognostic Risk Stratification in Acute Ischemic Stroke: A Preliminary Study
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
ABSTRACT Aims To preliminarily characterize metabolic molecular subtypes of cerebral thromboemboli and evaluate their clinical significance in anterior circulation acute ischemic stroke due to large vessel occlusion (AIS‐LVO). cns71116-sec-0001 Methods Untargeted metabolomics was performed on thromboemboli retrieved from 36 patients with anterior circulation AIS‐LVO using ultra‐performance coupled liquid chromatography with quadrupole time‐of‐flight mass spectrometry (UPLC‐Q‐TOF‐MS). Unsupervised hierarchical clustering was employed to identify distinct metabolic molecular subtypes, and their associations with stroke etiology, radiographic severity, and functional outcomes were analyzed. cns71116-sec-0002 Results Two distinct thrombus metabolic molecular subtypes (C1 and C2) were identified based on 12 metabolites significantly associated with both short‐term (7‐day ∆NIHSS) and long‐term (90‐day mRS) functional outcomes. The C1 subtype, predominantly cardioembolic, exhibited enhanced lipid metabolism, whereas the C2 subtype, primarily atherothrombotic, demonstrated increased folate metabolism. Patients with C1 thromboemboli presented more severe admission ischemic lesions (as indicated by ASPECTS) and experienced poorer short‐term and long‐term outcomes. A six‐metabolite signature derived from LASSO regression was identified for exploratory discrimination of thrombus metabolic subtypes, etiological subtypes, and 90‐day outcomes. cns71116-sec-0003 Conclusion This preliminary e
Abstract
ABSTRACT Aims To preliminarily characterize metabolic molecular subtypes of cerebral thromboemboli and evaluate their clinical significance in anterior circulation acute ischemic stroke due to large vessel occlusion (AIS‐LVO). cns71116-sec-0001 Methods Untargeted metabolomics was performed on thromboemboli retrieved from 36 patients with anterior circulation AIS‐LVO using ultra‐performance coupled liquid chromatography with quadrupole time‐of‐flight mass spectrometry (UPLC‐Q‐TOF‐MS). Unsupervised hierarchical clustering was employed to identify distinct metabolic molecular subtypes, and their associations with stroke etiology, radiographic severity, and functional outcomes were analyzed. cns71116-sec-0002 Results Two distinct thrombus metabolic molecular subtypes (C1 and C2) were identified based on 12 metabolites significantly associated with both short‐term (7‐day ∆NIHSS) and long‐term (90‐day mRS) functional outcomes. The C1 subtype, predominantly cardioembolic, exhibited enhanced lipid metabolism, whereas the C2 subtype, primarily atherothrombotic, demonstrated increased folate metabolism. Patients with C1 thromboemboli presented more severe admission ischemic lesions (as indicated by ASPECTS) and experienced poorer short‐term and long‐term outcomes. A six‐metabolite signature derived from LASSO regression was identified for exploratory discrimination of thrombus metabolic subtypes, etiological subtypes, and 90‐day outcomes. cns71116-sec-0003 Conclusion This preliminary exploratory study identifies two metabolically distinct thrombus molecular subtypes with clinical implications in anterior circulation AIS‐LVO, providing a novel basis for risk stratification and personalized secondary prevention and warrants further investigation. cns71116-sec-0004 This study identified two metabolically distinct thrombus molecular subtypes in AIS: a lipid metabolism‐enriched subtype (C1) associated with cardioembolic stroke and poor functional outcomes, and a folate metabolism‐enriched subtype (C2) linked to atherothrombotic stroke and better prognosis. A six‐metabolite signature further demonstrated exploratory potential for discriminating thrombus metabolic molecular subtypes, etiological subtypes, and 90‐day functional outcomes. graphical