基于泛凋亡相关基因分析颅内动脉瘤发生机制并构建诊断模型OA

Objective This study aimed to identify differentially expressed PANoptosis-related genes involved in intracranial aneurysm,explore their mechanisms related to aneurysm formation and rupture,and construct a diagnostic model. Methods Six data sets of GSE54083,GSE122897,GSE36791,GSE75436,GSE6551,GSE13353 and PANoptosis-related genes were obtained from the gene expression omnibus(GEO)and GeneCards databases,respectively.R 4.3.1 was used to analyze the GSE54083 data set to identify the intersection of differentially expressed genes and PANoptosis-related genes in intracranial aneurysms,and then the differentially expressed PANoptosis-related genes were further screened in GSE54083 and GSE75436.Functional enrichment analysis of differentially expressed genes was performed using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis methods.Least absolute shrinkage and selection operator(LASSO)regression was used to construct a diagnostic model and identify key genes,and the diagnostic model performance was verified internally and externally in the data sets GSE54083,GSE75436,GSE122897,GSE6551 and GSE13353,respectively.The immune infiltration of each sample in GSE54083 was evaluated by CIBERSORT algorithm.The search tool for the retrieval of interacting genes/proteins(STRING)database was used to search for three key genes of toll like receptor 4(TLR4),ATP-binding cassette transporter B1(ABCB1)and caspase activation and recruitment domain 16(CARD16)to construct a protein-protein interaction network and explore the interaction among key genes. Results A total of 119 differentially expressed PANoptosis related genes(71 up-regulated and 48 down-regulated)were identified in this study,which were enriched in MAPK,ERK1/ERK2,PKB and I-κB kinase/NF-κB signaling pathways,and were associated with focal adhesion,cytoskeleton and nuclear membrane.Through two independent data sets screening and LASSO regression,three key genes(TLR4,ABCB1,CARD16)were obtained.Immune infiltration analysis showed that the proportion of memory B cells,CD8+T cells,memory activated CD4+memory activated T cells,regulatory T cell and eosinophils increased in patients with intracranial aneurysms,while the proportion of plasma cells,naive CD4+T cells,follicular helper T cell,activated natural killer cells,M0/M2 macrophages,activated dendritic cells,mast cells and neutrophils decreased.Protein-protein interaction network analysis showed that the three key genes were involved in an interaction network containing 53 nodes and 196 edges.The LASSO diagnostic model based on the above three key genes showed good predictive performance in both the internal validation set(AUC 0.949,0.920 respectively)and the external validation set(AUC 0.713,0.837 respectively). Conclusions This study systematically revealed the key role of PANoptosis-related genes in intracranial aneurysms,and established the value of TLR4,CARD16 and ABCB1 as potential biomarkers.These findings not only deepen the understanding of the pathological mechanism of intracranial aneurysms,but also provide a new theoretical basis for the development of accurate diagnosis and treatment strategies for intracranial aneurysms based on PANoptosis.Future studies can further explore the specific regulatory mechanisms and clinical transformation potential of these genes in the development of intracranial aneurysms.