Identification of Circular RNA hsa_circ_0001599 as a Novel Biomarker for Large-Artery Atherosclerotic Stroke

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Circular RNAs (circRNAs) are a recently discovered noncoding RNA isoform capable of regulating neurological disease incidence. The present study was designed to characterize the circRNA expression profiles present in large-artery atherosclerosis (LAA)-type acute ischemic stroke patients and to detect biomarkers suitable for LAA-stroke detection. Using a RNA-seq-based approach, we characterized circRNA expression profiles in five LAA-stroke patients and four controls. We confirmed the differential expression of target circRNAs through quantitative real-time polymerase chain reaction (qRT-PCR), and used Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses to explore their functional roles. The diagnostic value of specific circRNAs was evaluated through a receiver operating characteristic (ROC) curve analysis. We identified 182 upregulated and 176 downregulated circRNAs in LAA-stroke patients and confirmed the differential expression of six circRNAs through qRT-PCR. These differentially expressed circRNAs are primarily associated with chromatin modification, autophagy, platelet activation, and neural precursor cell proliferation. The hsa_circRNA_0001599 expression levels were positively correlated with the National Institutes of Health Stroke Scale scores and infarct volumes, with an ROC analysis of hsa_circRNA_0001599 in LAA-stroke, yielding an area under the curve of 0.805 (95% confidence interval: 0.748–0.862; p < 0.001), consistent with sensitivity and specificity values of 64.41% and 89.93%, respectively, for the diagnosis of LAA-stroke. A transcriptome-wide survey of differential circRNA expression in LAA-stroke patients revealed hsa_circRNA_0001599 as a putative circRNA biomarker of LAA-stroke diagnosis.

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