ABSTRACT NUMBER: ESOC2026A805 PROTEOMIC DISCOVERY AND CLINICAL VALIDATION OF STROKE BIOMARKERS HPX AND HSP27

Abstract Background and aims Ischemic stroke is a leading cause of mortality and long-term disability. Despite the efficacy of intravenous thrombolysis and mechanical thrombectomy, their use is limited by narrow therapeutic windows and strict eligibility criteria. Blood-based biomarkers could improve early diagnosis, stroke subtype classification, and prognosis. This study aimed to identify biomarkers associated with infarct topography, combining proteomic discovery in experimental models with clinical validation in patients. Methods Proteomic analysis of ischemic brain tissue was performed in a rat model of stroke using liquid chromatography–tandem mass spectrometry. Candidate proteins were selected based on differential expression and subsequently assessed in retrospective serum samples from patients with cortical–subcortical stroke (CSS, n=58) and subcortical stroke (SS, n=34), collected at 24 hours and 3 months post-stroke, and compared with controls (n=19). Results Three proteins, hemopexin (HPX), heat shock protein beta-1 (HSP27), and alpha-1 antitrypsin (A1AT), were altered in ischemic brain tissue and detectable in patient serum. HPX and HSP27 discriminated between CSS and SS with significant differences and good diagnostic performance. A1AT showed higher inter-individual variability and only a non-significant trend toward elevation in SS. Conclusions HPX and HSP27 emerged as candidate biomarkers reflecting infarct topography in ischemic stroke. Their consistent profiles across acute and post-acute phases support their potential for patient stratification and for guiding more personalized therapeutic strategies. Conflict of interest Nothing to disclose