UPP1 is a dual biomarker of prognosis and immune microenvironment in IDH wild-type glioblastoma.

Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumor. Current therapies (temozolomide/radiotherapy) often encounter resistance, necessitating novel molecular targets. Bioinformatics analysis was performed for the data obtained from TCGA, COSMIC, cbioPortal, and MethSurv databases. Tools such as GO, KEGG, GSEA, ROC, and protein-protein interactions (PPI) were employed to investigate the role that UPP1 has on GBM. The effects of UPP1 were further validated using RT-PCR and Western blotting(WB). UPP1 overexpression correlated with poor survival (P < 0.05) and immunosuppression, showing positive associations with immune infiltrates (Tregs, DCs, Th1/Th17 cells) and inflammation-related pathway activation. Silencing UPP1 suppressed proliferation (P < 0.001) in glioma cells. Several DNA methylation patterns of UPP1(8 CpG sites, e.g., cg07703017) were identified as having significant prognostic value. UPP1 drives immunosuppression and serves as a dual biomarker: expression levels stratify prognosis, while methylation profiles offer therapeutic insights. Its immunometabolic regulation positions UPP1 as a promising target for GBM precision therapy.