Identification of immune-infiltrated hub genes as potential biomarkers of Moyamoya disease by bioinformatics analysis
Abstract Background Moyamoya disease (MMD) is a unique chronic progressive cerebrovascular disease. The molecular mechanism behind pathophysiology is still elusive. This study aims to determine the key genes and their roles in the immune infiltration of MMD.Methods We download raw gene expression profiles (GSE157628, GSE141024) of cerebrovascular tissue from GEO database. Identify differentially expressed genes (DEGs) and perform functional enrichment analysis. The CIBERSORT deconvolution algorithm was used to analyze the proportion of immune cell infiltration between MMD and negative control group. We screened for neutrophil-associated DEGs, constructed a protein-protein interaction network (PPI) using STRING, and clarified hub genes using the Cytoscape plugin MCODE analysis. The receiver operating characteristic (ROC) curve is applied to test and filter the best gene signature.Results A total of 570 DEGs were detected, including 212 downregulated and 358 up-regulated genes. Reactome and KEGG enrichment revealed that DEGs are involved in the cell cycle, molecular transport, and metabolic pathways. The immune infiltration profile demonstrates that MMD cerebrovascular tissues contained a higher proportion of neutrophils, monocytes, and NK cells than negative control group. PPI network and MCODE cluster identified 9 DEGs (UNC13D, AZU1, PYCARD, ELANE, SDCBP, CCL11, CCL15, CCL20, and CXCL5) associated with neutrophil infiltration. ROC results showed that UNC13D has good specificity and sensitivity (AUC = 0.7846).Conclusions The characteristics of immune infiltration in the cerebrovascular tissues of MMD patients and abnormal expression of hub genes provide new insights for understanding MMD progression. UNC13D is promising to be one of the candidate molecules to determine neutrophil infiltration characteristics in MMD.