From genes to diagnosis: The impact of UNC5B and DOK5 in intracranial aneurysm detection and pathogenesis

Objective: Intracranial aneurysms exhibit a notable prevalence within the general population, characterized by an incidence rate ranging from 1% to 2% and an annual rupture rate of approximately 16.4 per 100,000 individuals.Genes that are diagnostic and therapeutic are being investigated in this study linked to intracranial aneurysms by integrating machine learning, immune infiltration analysis, and single-gene sequencing. Methods: Differentially expressed genes (DEGs) were identified based on microarray data from the Gene Expression Omnibus (GEO) database between individuals with intracranial aneurysms and healthy controls.The DEGs were functionally analyzed using Gene Ontology (GO),Disease Ontology (DO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.Diagnostic biomarkers were identified and validated using machine learning algorithms and confirmed with external validation datasets.Subsequently, circulating biomarkers were assessed, and immune cell infiltration analysis along with single-cell sequencing were employed to elucidate the functional roles of the selected diagnostic biomarkers. Results: It was found that intracranial aneurysm patients and healthy controls shared 13,101 DEGs, with 1,108 genes upregulated and 969 downregulated.Aneurysms containing intracranial aneurysms showed significant immunoresponse-related enrichment in GO,DO,and KEGG pathway analyses.Technologies based on machine learning, such as LASSO, Random Forest, and SVM-RFE(Support Vector Machine-Recursive Feature Elimination), identified UNC5B and DOK5 as potential diagnostic biomarkers with high efficacy. Immune cell infiltration analysis indicated an elevated presence of various immune cells in intracranial aneurysms, particularly M1 macrophages.The UNC5B gene expression in fibroblasts is linked to intracranial aneurysm pathogenesis. Conclusion: In conclusion, the UNC5B and DOK5 genes emerge as potential diagnostic biomarkers for intracranial aneurysms.There is a positive correlation between UNC5B expression and M1 macrophages and it is primarily found in fibroblasts, suggesting that increased M1 macrophages and UNC5B expression in fibroblasts may contribute to intracranial aneurysm pathogenesis.