Identification and validation of a pyroptosis-related gene signature in intracranial aneurysm

Intracranial aneurysm (IA) is a life-threatening cerebrovascular disorder, the underlying molecular mechanisms of which remain incompletely elucidated. Pyroptosis, a pro-inflammatory form of programmed cell death, has been implicated in various vascular pathologies. However, its role in the pathogenesis of IA remains largely unclear. In this study, we identified and validated a pyroptosis-related gene signature linked to IA using GEO dataset. Differential expression analysis and pathway enrichment methods revealed key pyroptosis-related markers, including CASP8, NOD2, PYCARD, which were strongly associated with IA progression. Functional analysis highlighted their involvement in inflammatory and immune pathways, particularly in promoting vascular remodeling through pyroptosis-driven mechanisms. Machine learning approaches refined these markers into a robust predictive signature. Validation in independent cohorts confirmed their diagnostic and prognostic potential for IA. Moreover, we validated the upregulation of these genes and found the activation of CASP8 in clinical IA samples. Our findings provide novel insights into the molecular underpinnings of IA, offering a framework for the development of pyroptosis-based biomarkers and therapeutic strategies aimed at early detection and targeted intervention in IA management.