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

The prevalence of intracranial aneurysms (IAs) has increased globally. We performed bioinformatics analysis to identify key biomarkers associated with IA formation. 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. 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. © 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Citation

Shifu Li, Qian Zhang, Zheng Huang, Fenghua Chen. Integrative analysis of multi-omics data to identify three immune-related genes in the formation and progression of intracranial aneurysms. Inflammation research : official journal of the European Histamine Research Society ... [et al.]. 2023 May;72(5):1001-1019

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PMID: 37014439

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