Hypertension-driven mechano-immune crosstalk related novel genes may be potential targets for IA rupture progression

Integrated genomic and transcriptomic analyses were employed to identify novel molecular targets and elucidate underlying mechanisms in the progression from unruptured to ruptured intracranial aneurysms (IAs). The study integrated differentially expressed genes identified through GWAS-based SNP screening and transcriptomic analysis of three independent datasets (GSE13353, GSE26969, GSE75436). Protein-protein interaction network construction and functional enrichment analysis of overlapping genes revealed two key interactions: ITGAX-JAM3 and KLHL28-TOGARAM1, with ITGAX and MAGI2 emerging as consensus genes across all datasets. Machine learning-based prioritisation via LASSO regression with L1 penalty selected optimal characteristic genes, validated through ROC curve analysis (AUC > 0.85). These findings demonstrate that ITGAX, JAM3, KLHL28, TOGARAM1, and MAGI2 represent promising molecular targets worthy of further investigation in the context of hypertension-driven mechano-immune crosstalk during IA rupture progression, providing new insights for both mechanistic studies and clinical management strategies.