Novel Insights into the Potential Diagnostic Value of Circulating Exosomal IncRNA-Related Networks in Large Artery Atherosclerotic Stroke

Abstract

Exosomes show diagnostic and therapeutic promise as carriers of ncRNAs in diseases. LncRNAs in exosomes have been identified as being stable and avoided degradation by nucleolytic enzymes. Although lncRNAs have been confirmed to be important in cancers, no studies for exo-lncRNAs have been reported in LAA stroke. High-throughput sequencing was performed to detect the differential expression profiles of lncRNAs in five paired plasma-derived exosome samples from patients with LAA stroke and controls (matched on vascular risk factors). Exo-lncRNA-associated networks were predicted with a combination of multiple databases. The expression of the selected genes in the networks was confirmed by qRT-PCR in a validation set (LAA vs. controls = 30:30). Furthermore, ROC analysis was used to evaluate the diagnostic performance of the lncRNA-related networks. A total of 1,020 differentially expressed lncRNAs were identified in LAA stroke patients. GO and KEGG pathway analyses indicated that their target genes are involved in atherosclerosis-related pathways, including inflammation, cell adhesion, and cell migration. qRT-PCR confirmed that the expression trend of differential expressed genes was consistent with RNA-seq. Furthermore, the AUCs of the lnc_002015-related network and lnc_001350-related network were 0.959 and 0.97, respectively, in LAA stroke. Our study showed the differential expression of lncRNAs in plasma exosomes and presented related diagnostic networks for LAA stroke for the first time. The results suggested that exosomal lncRNA-related networks could be potential diagnostic tools in LAA stroke.