Utilizing RNA sequencing to identify gene expression markers of stroke-causing thrombi origin: A pilot study

Area of Science:

• Neuroscience
• Genomics
• Biomarker Discovery

Background:

• Cryptogenic stroke, with an unknown embolic source in 30-40% of cases, presents a diagnostic challenge.
• Mechanical thrombectomy for acute large vessel occlusion stroke enables direct retrieval and analysis of thrombi.
• High-throughput RNA sequencing (RNAseq) offers a method to analyze gene expression within these retrieved clots.

Purpose of the Study:

• To investigate the feasibility of using RNA sequencing to analyze gene expression in cerebral thrombi.
• To identify potential genetic markers that can differentiate stroke origins, particularly for cryptogenic embolisms.
• To compare gene expression profiles between thrombi from patients with carotid stenosis and atrial fibrillation.

Main Methods:

• A prospective study involving RNA sequencing of cerebral thrombi from acute ischemic stroke patients.
• Thrombi samples were categorized into 'Carotid group' (ipsilateral >70% carotid stenosis) and 'Atrial Fibrillation (AF)' group.
• Differential gene expression analysis was performed between the two groups using RNAseq.

Main Results:

• RNA sequencing successfully analyzed 8 cerebral thrombi (4 Carotid, 4 AF).
• 131 genes exhibited significant differential expression (FDR ≤ 0.05, fold change ≥ 2) between the groups.
• Candidate biomarkers HSPA1B and GPRC5B showed the greatest expression fold differences, with 26 genes selected overall.

Conclusions:

• RNA sequencing of acute ischemic stroke thrombi is a feasible technique.
• Novel potential biomarkers were identified for determining stroke-causing thrombi origin.
• This approach shows promise for diagnosing the cause of cryptogenic strokes.