Identification of immune-infiltrated hub genes as potential biomarkers of Moyamoya disease by bioinformatics analysis

Orphanet Journal of Rare Diseases

Fa Jin¹  Chuanzhi Duan¹ 

[1] The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory On Brain Function Repair and Regeneration, Department of Cerebrovascular Surgery, Neurosurgery Center, Zhujiang Hospital, Southern Medical University, 510282, Guangzhou, China;

关键词: Moyamoya disease;    Immune infiltration;    Neutrophils;    UNC13D;    Bioinformatics analysis;   

DOI  :  10.1186/s13023-022-02238-4

来源: Springer

【 摘 要 】

BackgroundMoyamoya disease (MMD) is a rare chronic progressive cerebrovascular disease. Recent studies have shown that autoimmune inflammation may also be an important pathology in MMD but the molecular mechanisms of inflammation in this disease are still large unknown. This study was designed to identify key biomarkers and the immune infiltration in vessel tissue of MMD using bioinformatics analysis.MethodsRaw gene expression profiles (GSE157628, GSE141024) were downloaded from the Gene Expression Omnibus (GEO) database, identified differentially expressed genes (DEGs) and performed functional enrichment analysis. The CIBERSORT deconvolution algorithm was used to analyze the proportion of immune cells between MMD and an MMD-negative control group. We screened for neutrophil-associated DEGs, constructed a protein–protein interaction network (PPI) using STRING, and clarified the gene cluster using the Cytoscape plugin MCODE analysis. The receiver operating characteristic (ROC) curve was applied to test and filter the best gene signature.ResultsA total of 570 DEGs were detected, including 212 downregulated and 358 up-regulated genes. Reactome and KEGG enrichment revealed that DEGs were involved in the cell cycle, molecular transport, and metabolic pathways. The immune infiltration profile demonstrated that MMD cerebrovascular tissues contained a higher proportion of neutrophils, monocytes, and natural killer cells in MMD than in controls. The PPI network and MCODE cluster identified nine 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).ConclusionsThe 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 shows promise as a candidate molecule to determine neutrophil infiltration characteristics in MMD.

【 授权许可】

CC BY