• Shubham Misra, Praveen Singh, Shantanu Sengupta, Manoj Kushwaha, Zuhaibur Rahman, Divya Bhalla, Pumanshi Talwar, Manabesh Nath, Rahul Chakraborty, Pradeep Kumar, Amit Kumar, Praveen Aggarwal, Achal K Srivastava, Awadh K Pandit, Dheeraj Mohania, Kameshwar Prasad, Nishant K Mishra, and Deepti Vibha.
• Department of Neurology, All India Institute of Medical Sciences, New Delhi, India.
• Eur. J. Clin. Invest. 2024 Dec 10: e14372e14372.

BackgroundRapid diagnosis of stroke and its subtypes is critical in early stages. We aimed to discover and validate blood-based protein biomarkers to differentiate ischemic stroke (IS) from intracerebral haemorrhage (ICH) using high-throughput proteomics.MethodsWe collected serum samples within 24 h from acute stroke (IS & ICH) and mimics patients. In the discovery phase, SWATH-MS proteomics identified differentially expressed proteins, which were validated using targeted proteomics in the validation phase. We conducted interaction network and pathway analyses using Cytoscape 3.10.0. We determined cut-off points using the Youden Index. We developed three prediction models using multivariable logistic regression analyses. We assessed the model performance using statistical tests.ResultsWe included 20 IS and 20 ICH in the discovery phase and 150 IS, 150 ICH, and six stroke mimics in the validation phase. We quantified 375 proteins using SWATH-MS. Between IS and ICH, we discovered 20 differentially expressed proteins. In the validation phase, the combined prediction model including three biomarkers: GFAP (aOR 0.04; 95%CI .02-.11), MMP-9 (aOR .09; .03-.28), APO-C1 (aOR 5.76; 2.66-12.47) and clinical variables independently differentiated IS from ICH (accuracy: 92%, negative predictive value: 94%). Adding biomarkers to clinical variables improved discrimination by 26% (p < .001). Additionally, nine biomarkers differentiated IS from ICH within 6 h, while three biomarkers differentiated IS from mimics.ConclusionsOur study demonstrated that GFAP, MMP-9 and APO-C1 biomarkers independently differentiated IS from ICH within 24 h and significantly improved the discrimination ability of prediction models. Temporal profiling of these biomarkers in the acute phase of stroke is warranted.© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

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