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Integrative analysis of multi-omics data to identify three immune-related genes in the formation and progression of intracranial aneurysms

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Abstract

Objective and design

The prevalence of intracranial aneurysms (IAs) has increased globally. We performed bioinformatics analysis to identify key biomarkers associated with IA formation.

Methods and results

We conducted a comprehensive analysis combined with multi-omics data and methods to identify immune-related genes (IRGs) and immunocytes involved in IAs. Functional enrichment analyses showed enhanced immune responses and suppressed organizations of extracellular matrix (ECM) during aneurysm progression. xCell analyses showed that the abundance of B cells, macrophages, mast cells, and monocytes significantly increased from levels in control to unruptured aneurysms and to ruptured aneurysms. Of 21 IRGs identified by overlapping, a three-gene (CXCR4, S100B, and OSM) model was constructed through LASSO logistic regression. The diagnostic ability of the three biomarkers in discriminating aneurysms from the control samples demonstrated a favorable diagnostic value. Among the three genes, OSM and CXCR4 were up-regulated and hypomethylated in IAs, while S100B was down-regulated and hypermethylated. The expression of the three IRGs was further validated by qRT-PCR and immunohistochemistry and mouse IA model using scRNA-seq analysis.

Conclusion

The present study demonstrated heightened immune response and suppressed ECM organization in aneurysm formation and rupture. The three-gene immune-related signature (CCR4, S100B, and OSM) model may facilitate IA diagnosis and prevention.

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Availability of data and material

GEO belongs to public databases. The patients involved in the database have obtained ethical approval. Users can download relevant data for free for research and publish relevant articles. The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.

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Acknowledgements

We acknowledge GEO databases for providing their platforms and contributors for uploading their meaningful datasets.

Funding

This study did not receive any funding or financial support.

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Authors and Affiliations

  1. Department of Neurosurgery, Xiangya Hospital, Central South University, 87 Xiangya Street, Changsha, 410008, Hunan, China

    Shifu Li, Qian Zhang, Zheng Huang & Fenghua Chen

  2. National Clinical Research Center for Geriatric Disorders, Central South University, 87 Xiangya Street, Changsha, 410008, Hunan, China

    Shifu Li, Qian Zhang, Zheng Huang & Fenghua Chen

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  1. Shifu Li
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  2. Qian Zhang
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  3. Zheng Huang
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Contributions

Conceptualization, SL and QZ; methodology, SL; software, SL; validation, SL; formal analysis, SL; investigation, SL; writing—original draft preparation, SL; writing—review and editing, QZ; visualization, ZH; supervision, FC; all authors have read and agreed to the published version of the manuscript.

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Correspondence to Fenghua Chen.

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The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.

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Written informed consent was obtained from each participants and this study was approved by the Institutional Review Board of Xiangya Hospital (202103613).

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Li, S., Zhang, Q., Huang, Z. et al. Integrative analysis of multi-omics data to identify three immune-related genes in the formation and progression of intracranial aneurysms. Inflamm. Res. 72, 1001–1019 (2023). https://doi.org/10.1007/s00011-023-01725-z

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