A Two-Gene-Based Diagnostic Signature for Ruptured Intracranial Aneurysms.

Ruptured intracranial aneurysm (IA) is a disease with high mortality. Despite the great progress in treating ruptured IA, methods for risk assessment of ruptured IA remain limited. In this study, we aim to develop a robust diagnostic model for ruptured IA. Gene expression profiles in blood samples of 18 healthy persons and 43 ruptured IA patients were obtained from the Gene Expression Omnibus (GEO). Differential expression analysis was performed using limma Bioconductor package followed by functional enrichment analysis clusterProfiler Bioconductor package. Immune cell compositions in ruptured IA and healthy samples were assessed through the CIBERSORT tool. Protein-protein interaction (PPI) was predicted based on the STRING database. Logistic regression model was used for the construction of predictive model for distinguishing ruptured IA and healthy samples. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to validate the gene expression between the ruptured IA and healthy samples. A total of 58 differentially expressed genes (DEGs) were obtained for ruptured IA patients compared with healthy controls. Functional enrichment analysis showed that the DEGs were enriched in biological processes related to neutrophil activation, neutrophil degranulation, and cytokine-cytokine receptor interaction. Notably, immune analysis results proved that the rupture of IA might be related to immune cell distribution. We further identified 24 key genes as hub genes using the PPI networks. The logistic regression model trained based on the 24 key genes ultimately retained two genes, i.e., IL2RB and CCR7, which had great potential for risk assessment for rupture of IA. The RT-qPCR further validated that compared with the healthy samples, the expression levels of IL2RB and CCR7 were decreased in ruptured IA samples. This study might be helpful for cohorts who have a high risk of ruptured IA for early diagnosis and prevention of the disease.