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Bioinformatics Gene Analysis of Potential Biomarkers and Therapeutic Targets for Unstable Atherosclerotic Plaque-Related Stroke

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Abstract

Atherosclerotic plaque instability is a major cause of ischemic stroke. Researchers must develop novel strategies for the detection and treatment of unstable atherosclerotic plaque (UAP)-related stroke. We aimed to identify potential biomarkers and therapeutic targets of UAP-related stroke. Differentially expressed genes (DEGs) of UAP, ischemic stroke and smoking were identified by microarray analyses from the Gene Expression Omnibus. Gene Ontology (GO) and pathway functional enrichment analyses of DEGs were performed to analyze plaque destabilization and ischemic stroke physiopathology. An integrative analysis of UAP, ischemic stroke and smoking DEGs and functional annotations was performed to identify the underlying physiopathology and hub genes in UAP-related stroke and the relationship with smoking. Online search databases were applied to confirm hub gene biofunctions and their relationships with atherosclerosis and cerebrovascular diseases. Following integrative analysis, 18 co-DEGs of UAP and ischemic stroke, including 17 upregulated and one downregulated, were identified. Inflammation, immunity, extracellular matrix degradation, blood coagulation, apoptosis and nerve degeneration were the primary physiopathological processes in UAP-related stroke. Hub genes included MMP9, ITGAM, CCR1, NCF2 and CD163, among which MMP9 and ITGAM were top 10 genes for both UAP and stroke. Smoking may upregulate MMP9, NCF2, C5AR1 and ANPEP to accelerate plaque destabilization and UAP-related stroke. MMP9, ITGAM, CCR1, NCF2, CD163, hsa-miR-3123 and hsa-miR-144-3p are potential diagnostic and prognostic biomarkers of UAP-related stroke. MMP9 and ITGAM are potential therapeutic targets of UAP-related stroke, which will contribute to the development of novel management strategies.

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Availability of Data and Material

The data used in this study were downloaded from the GEO database. The data used to support the findings of this study are available from corresponding websites upon request.

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Acknowledgments

This study used the GEO database as a data source. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the National Center for Biotechnology Information (NCBI) for the creation and distribution of the GEO database.

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Authors and Affiliations

  1. Shantou University Medical College, Shantou, Guangdong, China

    Shaojiong Zhou

  2. Neurology Department, First Affiliated Hospital of Shantou University Medical College, No.57, ChangPing Road, JinPing District, ShanTou City, 515041, Guangdong Province, China

    Shaojiong Zhou, Shuo Liu, Xiaoqiang Liu & Weiduan Zhuang

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  1. Shaojiong Zhou
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  2. Shuo Liu
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Contributions

Shaojiong Zhou and Shuo Liu analyzed and interpreted the data. Xiaoqiang Liu participated in the study. Shaojiong Zhou and Shuo Liu wrote the manuscript. Shaojiong Zhou and Xiaoqiang Liu conceived and designed the study. Weiduan Zhuang supervised the study and provided financial support. All authors read and approved the final manuscript.

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Correspondence to Weiduan Zhuang.

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Electronic supplementary material

Supplementary Material 1

Gene Ontology term enrichment analyses of UAP-DEGs, ischemic stroke-DEGs and smoking-DEGs. (XLSX 24 kb)

Supplementary Material 2

Pathways enrichment analyses of UAP-DEGs, ischemic stroke-DEGs and smoking-DEGs. (XLSX 51 kb)

Supplementary Material 3

Functional enrichment analyses of co-DEGs of UAP and ischemic stroke. (XLSX 16 kb)

Supplementary Material 4

Gene Ontology Consortium annotations of hub genes of UAP-related stroke. (XLSX 20 kb)

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Zhou, S., Liu, S., Liu, X. et al. Bioinformatics Gene Analysis of Potential Biomarkers and Therapeutic Targets for Unstable Atherosclerotic Plaque-Related Stroke. J Mol Neurosci 71, 1031–1045 (2021). https://doi.org/10.1007/s12031-020-01725-2

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