Small RNA Signatures of Acute Ischemic Stroke in L1CAM Positive Extracellular Vesicles

Authors

Bharti Manwani
Nivetha Brathaban
Abiya Baqai
Yashee Munshi
Hilda W Ahnstedt
Mengqi Zhang
Kajsa Arkelius
Ted Llera
Edilberto Amorim
Fanny M Elahi
Neel S Singhal

Publication Date

6-12-2024

Journal

Scientific Reports

Abstract

L1CAM-positive extracellular vesicles (L1EV) are an emerging biomarker that may better reflect ongoing neuronal damage than other blood-based biomarkers. The physiological roles and regulation of L1EVs and their small RNA cargoes following stroke is unknown. We sought to characterize L1EV small RNAs following stroke and assess L1EV RNA signatures for diagnosing stroke using weighted gene co-expression network analysis and random forest (RF) machine learning algorithms. Interestingly, small RNA sequencing of plasma L1EVs from patients with stroke and control patients (n = 28) identified micro(mi)RNAs known to be enriched in the brain. Weighted gene co-expression network analysis (WGCNA) revealed small RNA transcript modules correlated to diagnosis, initial NIH stroke scale, and age. L1EV RNA signatures associated with the diagnosis of AIS were derived from WGCNA and RF classification. These small RNA signatures demonstrated a high degree of accuracy in the diagnosis of AIS with an area under the curve (AUC) of the signatures ranging from 0.833 to 0.932. Further work is necessary to understand the role of small RNA L1EV cargoes in the response to brain injury, however, this study supports the utility of L1EV small RNA signatures as a biomarker of stroke.

Keywords

Humans, Extracellular Vesicles, Male, Ischemic Stroke, Neural Cell Adhesion Molecule L1, Female, Aged, Biomarkers, Middle Aged, Machine Learning, MicroRNAs

Comments

Supplementary Materials

Data Availability Statement

PMID: 38866905