Role of Circulating MicroRNAs as Biomarkers for Ischemic Stroke Patients With Type 2 Diabetes-Related Risk Factors

Stroke is the second leading cause of death globally. Acute Ischemic stroke (AIS), resulting from cerebral occlusions, constitutes the majority of incident stroke cases and is recurrently preceded by an episode of neuronal dysfunction referred to as transient ischemic attack (TIA). Pre-existing comorbid conditions such as type 2 diabetes (T2D) can also greatly affect disease prognosis and outcomes. However, currently, there are no robust blood biomarkers for diagnosis or prognosis of AIS. MicroRNAs (miRNAs) modulate various molecular pathways and have recently emerged as potential biomarkers for AIS. Herein, we conducted comprehensive circulating miRNA profiling of AIS patients (n=191) and compared it with circulating miRNA profiles of TIA patients (n=61) and healthy controls (n=93) to identify distinct circulating miRNAs. We also compared the miRNA profiles of AIS patients with T2D (n=92) with AIS patients without T2D (n=98). RNA-Seq was performed on serum samples, and robust analysis approaches were followed to identify distinct circulating miRNAs and investigate molecular pathways affected by the identified miRNAs. We identified 10 distinct miRNAs in AIS patients compared to healthy controls, including 5 miRNAs with possible diagnostic relevance and 11 with distinct regulatory profiles in AIS and TIA patients. Additionally, 5 miRNAs were identified in AIS patients with T2D as a comorbidity. Overall, these unique miRNA patterns have potential to serve as diagnostic and prognostic biomarkers for AIS. Moreover, our findings provide valuable insights into the specific miRNAs, associated molecular pathways, and potential clinical implications for individuals affected by AIS. Further investigations into the identified miRNA panels could pave the way for therapeutic targeting in clinical practice.