Objective To identify copper induced death-related subtypes of meningiomas and recognize key genes associated with disease-immune interactions.Methods Utilizing publicly available gene expression data related to meningiomas,differentially expressed acproptosis genes were screened.Subsequently,meningioma subtypes based on the expression values of these genes in tumor samples were identified.The differentially expressed genes between subtypes and their association with the tumor immune microenvironment were analyzed.Using immune cells with significant differences between subtypes as a phenotype,Weighted Gene Co-expression Network Analysis(WGCNA)was employed to screen disease-immune-related modules and extract module genes.Through intersection analysis,differentially expressed disease-immune-related genes were selected.Further analyses included protein-protein interaction(PPI)network analysis,functional enrichment analysis,Friends analysis,gene expression validation and correlation analysis between key genes and clinical factors.Results Differential expression of six copper death genes were detected,such as CDKN2 A and GLS,in meningiomas compared to normal samples,identifying two associated copper induced death subtypes.These subtypes encompassed 397 differentially expressed genes,including eight immune cell types.There were significant differences in immune cell infiltration between subtypes.WGCNA identified 282 disease-immune-related genes,and intersection analysis revealed 74 differentially expressed disease-immune-related genes.PPI and Friends analyses ultimately confirmed five key genes:LTBP1,LTBP2,and MFAP5,etc.Among these,LTBP2 and MFAP5 exhibited significant expression differences in meningioma grades.Western blot and immunohistochemistry validation demonstrated significant differences in MFAP5 expression between WHO Grade Ⅰ and WHO Grade Ⅲ,as well as WHO Grade Ⅰ and WHO Grade Ⅱ.Conclusions This study identifies two copper death-related meningioma subtypes characterized by differences in immune cell infiltration and immune responses.Key immune-related genes between these subtypes,such as LTBP2 and MFAP5,may represent critical mechanisms in the regulation of copper death in the occurrence and development of meningiomas,potentially serving as diagnostic biomarkers or immunotherapeutic targets for meningiomas.
维普
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