Serum MGP and ECP are commonly elevated in first-onset and recurrent ischemic stroke: a two-phase DIA proteomic study in a Chinese cold-region cohort.

Background: Ischemic stroke (IS) has a high recurrence rate, yet effective biomarkers for distinguishing first-onset from recurrent IS remain limited. This study aimed to identify serum proteomic biomarkers commonly elevated in both first-onset and recurrent IS and to evaluate their ability to discriminate each disease state from healthy controls in a Chinese cold-region population. Methods: The study was conducted in two phases. In the discovery phase, 10 patients with first-onset IS, 10 with recurrent IS, and 10 healthy controls were analyzed using Data-Independent Acquisition (DIA) proteomics; the validation phase expanded the sample to 49 patients with first-onset IS, 30 with recurrent IS, and 50 healthy controls. Differentially expressed proteins were defined as fold change≥1.5 or ≤0.67. Multivariable Firth penalized logistic regression adjusted for age and sex constructed diagnostic models, with data randomly split into training and test sets (2:1) for receiver operating characteristic (ROC) analysis. Results: Two core proteins were identified: matrix Gla protein (MGP) and eosinophil cationic protein (ECP). Both were significantly elevated in the first-onset and recurrent IS groups compared with healthy controls (all Conclusion: Serum MGP and ECP were commonly elevated in both first-onset and recurrent IS, and two separate combinatorial models discriminated each disease state from healthy controls with high accuracy. This biomarker panel covers three core pathological processes-atherosclerosis and vascular calcification, chronic inflammation, and hypercoagulable state-providing candidate biomarkers that warrant further investigation for disease-state characterization and risk stratification, particularly in high-latitude cold-region populations.