Potential Protein Signatures for Recurrence Prediction of Ischemic Stroke

Abstract

Background Acute ischemic stroke is a major cause of mortality and disability worldwide, with approximately 7.4% to 7.7% recurrence within the first 3 months. This study aimed to identify potential biomarkers for predicting stroke recurrence. Methods and Results We conducted a nested case–control study using a hospital‐based cohort from the Third China National Stroke Registry selecting 214 age‐ and sex‐matched patients with ischemic stroke with hypertension and no history of diabetes or heart disease. Using data‐independent acquisition for discovery and multiple reaction monitoring for quantitative validation, we identified 26 differentially expressed proteins in large‐artery atherosclerosis (Causative Classification of Ischemic Stroke [CCS]1), 16 in small‐artery occlusion (CCS3), and 25 in undetermined causes (CCS5) among patients with recurrent stroke. In the CCS1 and CCS3 subgroups, differentially expressed proteins were associated with platelet aggregation, neuronal death/cerebroprotection, and immune response, whereas differentially expressed proteins in the CCS5 subgroup were linked to altered metabolic functions. Validated recurrence predictors included proteins associated with neutrophil activity and vascular inflammation (TAGLN2 [transgelin 2], ITGAM [integrin subunit α M]/TAGLN2 ratio, ITGAM/MYL9 [myosin light chain 9] ratio, TAGLN2/RSU1 [Ras suppressor protein 1] ratio) in the CCS3 subgroup and proteins associated with endothelial plasticity and blood–brain barrier integrity (ITGAM/MYL9 ratio and COL1A2 [collagen type I α 2 chain]/MYL9 ratio) in the CCS3 and CCS5 subgroups, respectively. Conclusions These findings provide a foundation for developing a blood‐based biomarker panel, using causative classifications, which may be used in routine clinical practice to predict stroke recurrence.

Keywords

• plasma
• proteomics
• stroke recurrence