Study on differential gene expression profile of serum exosomes in patients with acute cerebral infarction

Abstract

ObjectiveTo analyze the differential gene expression profile of serum exosomes in patients with acute cerebral infarction (ACI) and clarify the changes in gene expression related to cerebral infarction injury and the potential serum markers. MethodsFour patients with ACI and five healthy people were enrolled in the Phase Ⅰ study. After serum isolation from peripheral blood, exosomes were extracted with exosomes kits, high-throughput detection of mRNA was performed with gene chips, and differentially expressed mRNAs were screened. Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed simultaneously. Furthermore, real-time polymerase chain reaction (qRT-PCR) was used to verify the expression levels of the screened differential mRNAs in the serum exosomes collected in Phase Ⅱ from 32 patients each in the ACI case and normal control groups. ResultsIn the Phase Ⅰ study, there were 248 differentially expressed mRNAs (fold change ≥ 2.0, P < 0.05) among five patients in the normal control group and four patients in the case group, of which the expression of 242 was upregulated and that of six was downregulated. The results of GO functional enrichment analysis mainly included behavior regulation, cell connection, and antioxidant activity. The results of KEGG pathway enrichment analysis mainly included ribosomes, proteasomes, oxytocin signaling pathways, and oxidative phosphorylation. After researching and screening based on relevant literature, it was found that among the genes with significant differential expression, H3F3B mRNA may be associated with and might play an important role in ACI. The qRT-PCR method was used to detect the H3F3B mRNA expression in serum exosomes of 32 patients each in the normal control and case groups in Phase Ⅱ; the expression was significantly higher in serum exosomes of the case group than in those of the normal control group (P < 0.001). H3F3B mRNA expression in serum exosomes of the case group positively correlated with age, the National Institutes of Health Stroke Scale (NIHSS) score, and the maximum infarct size (P < 0.05). ConclusionACI can lead to changes in the serum exosomes mRNA expression profile, which may be closely related to the occurrence, development, and prognosis of this condition. These findings will provide direction for research on the molecular mechanism, diagnostic markers, and therapeutic targets of ACI.