Immune-related genes construct and validate a risk model for aneurysm rupture leading to subarachnoid hemorrhage

Abstract

Abstract Background. Aneurysmal subarachnoid hemorrhage (aSAH) is an acute cerebrovascular illness with a pronounced rate of disability and fatality. Assessing the risk of rupture in unruptured intracranial aneurysms (UIAs) can guide early clinical intervention to avoid subarachnoid hemorrhage (SAH). Current methods to assess the occurrence of aSAH at the molecular level are inadequate. Numerous studies have shown that immunity and inflammation are the initiating factors of UIAs rupture, which provides a potential theoretical support for constructing a risk model for aSAH occurrence based on immune-related genes. Methods. GSE36791 containing 61 samples was used as the training set, and GSE73378 containing 226 samples was used as the validation set, and the above data sets were obtained from the Gene Expression Omnibus database. All samples were gene expression profiling from peripheral blood cells. Using R software to identify differential genes and key gene modules and explore the underlying biological processes of differential genes. Immune-related analyses were based on ssGSEA and CIBERSORT algorithms. Using Cox regression to fit the risk model for aSAH occurrence with 3 randomly selected immune-related genes, and validating the model in the test set. Result. A total of 22 hub genes were obtained by weighted gene co-expression network analysis and gene differential expression analysis. Functional enrichment analysis showed that hub genes were mainly enriched in immune and inflammation-related pathways. The results showed that neutrophils and monocytes made up the largest proportion of the samples. CD6, SLP and SLC2A11 were randomly selected to construct risk model for aSAH occurrence. Our analysis resulted in an AUC value of 0.859 for the training set and 0.627 for the validation set, indicating that the model has some accuracy and potential clinical application. Conclusion. We identified 22 key genes associated with immunity and randomly selected 3 genes to construct and validate a risk model for the development of SAH due to aneurysm rupture. We determined the likelihood of intracranial aneurysm rupture based on the model score. It is possible to quickly and conveniently guide whether early intervention is needed for unruptured aneurysms at the molecular level to prevent the formation of SAH and related complications. In addition, pivotal gene-mediated inflammation provides a new perspective for future studies on the mechanisms of aSAH initiation and subsequent neurological deterioration.