Integrated Analysis of Cuproptosis Regulators Reveals Prognostic Significance and Therapeutic Targets in IDH1 Mutant Glioma

Abstract

Glioma, characterized by significant heterogeneity and aggressiveness, poses a formidable therapeutic challenge. Cuproptosis, a newly identified form of regulated cell death driven by copper imbalance, has recently emerged as a pivotal factor in tumor biology. However, its role in IDH1-mutant gliomas remains poorly understood. Through comprehensive bioinformatics analysis of publicly available datasets, we identified two distinct subtypes of IDH1-mutant gliomas based on cuproptosis regulator expression profiles. Subtype G1 exhibited elevated PD-L1 expression, increased pro-tumor immune infiltration, and worse clinical outcomes, whereas subtype G2 was enriched in antitumor immune cells and associated with improved prognosis. We identified FDX1 and SLC31A1 as critical prognostic markers, with their upregulation linked to PD-L1 expression. Mechanistically, we delineated a ceRNA regulatory axis involving COX10-AS1/miR-1-3p/FDX1 and SLC31A1 that drives glioma progression. Building on these insights, we developed a prognostic risk model integrating FDX1 and SLC31A1 expression, demonstrating robust predictive accuracy for patient outcomes and potential utility in guiding individualized treatment strategies. These findings advance our understanding of the molecular landscape in IDH1-mutant gliomas and underscore the potential of cuproptosis regulators as novel therapeutic targets and biomarkers for precision oncology.