Development and validation of programmed cell death related genes in intracranial aneurysms

Intracranial aneurysm (IA) is a life-threatening condition. Programmed cell death (PCD) is central to aneurysm onset and progression. Nevertheless, a comprehensive analysis of the association between PCD and IA is lacking.We retrieved five IA-dataset including GSE13353, GSE15629, GSE26969, GSE54083, and GSE75436 from GEO database. After integrating these datasets, We calculated 9 cell death pattern scores via ssGSEA and identified ferroptosis and immunogenic cell death(ICD) as the higher relevance in the IA (AUC-ROC > 0.7).We relied on differential gene analysis and took intersections with ICD- and ferroptosis- genes, which was as the IA-PCD genes. Integrating Least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE), identified two key genes, namely NLRP3 and HMOX1. In the dataset, the two genes were significantly overexpressed in patients with IA. Immune infiltration analysis showed that NLRP3 and HMOX1 could influence the extent of immune cell infiltration.For further validation, we found that the expression levels of NLRP3 and HMOX1 in the serum of IA patients were significantly higher than those in the normal group though Elisa, consistenting with the bioinformatics result. In conclusion, NLRP3 and HMOX1 are associated with IA. These findings provide a basis for further exploring potential molecular driving mechanisms and screening suitable biomarkers.