Screening ferroptosis associated with glioblastoma prognosis and immunity based on bioinformatics / 安徽医科大学学报

ABSTRACT

Objective @#To investigate the molecular mechanism of ferroptosis in glioblastoma (GBM) and to provide insights for identifying new therapeutic targets . @*Methods @#GSE108474 was selected from gene expression omnibus (GEO) database and differentially expressed genes (DEGs ) in GBM were obtained by using GEO2R , compared with the gene set in the Ferroptosis database (FerrDb) to identify ferroptosis related gene . GO and KEGG enrich ment analyses were conducted using DAVID database . A protein-protein interaction network was created using String web site . Hub genes with high connectivity were confirmed using Cytoscape software . Prognostic and immune infiltration analyses were performed using TIMER web site . RNA expression levels and gene correlation analyses were carried out using GEPIA web site . Differential expression of hub gene proteins was analyzed by using the HPA database. Tumor immune characteristic correlations were examined using TISIDB database . Differences in mRNA expression of hub genes between tumor cells A172 and U251MG and normal astrocytes HA1800 were compared u sing the quantitative real time PCR @*Results @#Out of 5 331 differentially expressed genes , 114 were related to fer roptosis . GO and KEGG enrichment analysis suggested that these 114 genes might play roles in positive regulation of gene expression , and affect tumor progression through ferroptosis and autophagy pathways . 10 hub genes were i dentified in the protein protein interaction network , among which cluster of differentiation 44 ( CD44 ) , murine double minute 2 (MDM2) and signal transducer and activator of transcription 3 (STAT3) were found to be highly expressed in tumors with lower survival rates . CD44 , MDM2 and STAT3 mRNA expression were higher in GBM cells compared to normal cells . Protein expression of CD44 , MDM2 and STAT3 was higher in high grade glioma tis sues than that in normal tissues . The expression of three genes in the tumor was negatively correlated with ferropto sis . Immune infiltration analysis revealed that CD44 , MDM2 and STAT3 in the tumor were related to the infiltration of neutrophils , CD4 + T cells , and dendritic cells , and the expression of three genes was related to various chemo kines and their receptors .@*Conclusion @#CD44 , MDM2 and STAT3 may play a role in tumor ferroptosis and immune regulation , which have the potential to become a therapeutic target for GBM .