Identification of Circular RNA hsa_circ_0001599 as a Novel Biomarker for Large-Artery Atherosclerotic Stroke
Shengnan Li, Weidong Hu, Fu Deng, Shaofeng Chen, Peiyi Zhu, Mengxu Wang, Xinglan Chen, Ying Wang, Xingjuan Hu, Bin Zhao, Wangtao Zhong, Guoda Ma, You Li
Abstract
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.