Abstract

Stroke is a sudden cerebrovascular circulatory disorder with high morbidity, disability, mortality, and recurrence rate, but its pathogenesis and key genes are still unclear. In this study, bioinformatics was used to deeply analyze the pathogenesis of stroke and related key genes, so as to study the potential pathogenesis of stroke and provide guidance for clinical treatment. Gene Expression profiles of GSE58294 and GSE16561 were obtained from Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) were identified between IS and normal control group. The different expression genes (DEGs) between IS and normal control group were screened with the GEO2R online tool. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were performed. Using the Database for Annotation, Visualization and Integrated Discovery (DAVID) and gene set enrichment analysis (GSEA), the function and pathway enrichment analysis of DEGS were performed. Then, a protein–protein interaction (PPI) network was constructed via the Search Tool for the Retrieval of Interacting Genes (STRING) database. Cytoscape with CytoHubba were used to identify the hub genes. Finally, NetworkAnalyst was used to construct the targeted microRNAs (miRNAs) of the hub genes. A total of 85 DEGs were screened out in this study, including 65 upward genes and 20 downward genes. In addition, 3 KEGG pathways, cytokine − cytokine receptor interaction, hematopoietic cell lineage, B cell receptor signaling pathway, were significantly enriched using a database for labeling, visualization, and synthetic discovery. In combination with the results of the PPI network and CytoHubba, 10 hub genes including CEACAM8, CD19, MMP9, ARG1, CKAP4, CCR7, MGAM, CD79A, CD79B, and CLEC4D were selected. Combined with DEG-miRNAs visualization, 5 miRNAs, including hsa-mir-146a-5p, hsa-mir-7-5p, hsa-mir-335-5p, and hsa-mir-27a- 3p, were predicted as possibly the key miRNAs. Our findings will contribute to identification of potential biomarkers and novel strategies for the treatment of ischemic stroke, and provide a new strategy for clinical therapy.

Highlights

  • Stroke is a sudden disorder of cerebral blood circulation, including two types: ischemic stroke (IS) and hemorrhagic stroke [1]

  • In order to evaluate the potential molecular mechanism of regulating IS metastasis, differentially expressed genes (DEGs) was further analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis based on Database for Annotation, Visualization and Integrated Discovery (DAVID) and gene set enrichment analysis (GSEA) database

  • GSE58294 chip belonged to GPL570 platform, including 23 control samples and 69 samples, while GSE16561 chip belonged to GPL6882, including 24 control samples and 39 IS samples

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Summary

Introduction

Stroke is a sudden disorder of cerebral blood circulation, including two types: ischemic stroke (IS) and hemorrhagic stroke [1]. It is important to identify molecular targets for effective treatment of stroke and clarify the mechanism of brain injury. Bioinformatics analysis can use high-throughput gene sequencing technology to analyze the genome, transcriptome, and proteome information of organisms, and can reveal the mechanism of disease occurrence and development from various molecular levels, providing direction for laboratory and clinical research [8]. With the help of bioinformatics methods, differentially expressed genes (DEGs) were screened, and their functions and signal pathways were analyzed. By analyzing the biological functions related to IS, it could lay a foundation for the clinical diagnosis and treatment of IS. In order to evaluate the potential molecular mechanism of regulating IS metastasis, DEGs was further analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis based on Database for Annotation, Visualization and Integrated Discovery (DAVID) and gene set enrichment analysis (GSEA) database.

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