Comprehensive gene set enrichment and variation analyses identify as a potential prognostic biomarker for glioblastoma immunorelevance.

Glioblastoma (GBM) is the most common intracranial malignancy. encodes a histone H3 lysine 9 methyltransferase that acts as an oncogene in several cancers; however, its role in GBM remains unknown. We obtained GBM transcriptome and clinical data from The Cancer Genome Atlas (TCGA) database on the UCSC Xena platform to perform differential and enrichment analyses of genes in the high- and low-expression groups to construct a prognostic risk model. Analysis of related biological processes in GBM was performed by gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA). High- and low-risk subgroup mutation signatures were analyzed using maftools. Immune infiltration was evaluated using IOBR and CIBERSORT algorithms. We analyzed the cell types and intercellular communication networks in glioma stem cells (GSCs) using scRNA-seq. The effects on GBM cells and GSCs after inhibition of were investigated in vitro. was significantly overexpressed in GBM and associated with poor prognosis. -related differentially expressed genes were enriched in immune and inflammation related pathways, and GSEA revealed that these genes were significantly enriched in signaling pathways such as IL-18, oxidative phosphorylation, and regulation of TP53 activity. Mutational analysis revealed frequent alterations in TP53 and PTEN expression. In addition, the infiltration abundances of the five immune cell types were significantly different between the high- and low-expression groups. Analysis of cellular communication networks by scRNA-seq revealed a strong interaction between CRYAB-GSC and PTPRZ1-GSC in GSCs. In vitro experiments verified that knockdown of inhibited the viability and proliferation of U87 and U251 glioblastoma cells and downregulated the expression of stemness markers Nestin and SOX2 in CSC1589 and TS576 GSC lines. Increased expression is associated with immune cell infiltration and poor prognosis in patients with GBM. Inhibition of restrains GBM growth and reduces the stem cell properties of GSC. Thus, might be a prognostic predictor and immunotherapeutic target in patients with GBM.