Identification of Cuproptosis-Related Genes for Molecular Subtyping: Predicting Prognostic and Therapeutic Response in Glioma

作者：Xiaochun Xia, Xiaoying Huang, Longxiang Wu, Pengqin Xu, Peng Li · 发表于：OncoTargets and Therapy · 年份：2024 · DOI：10.2147/ott.s481443 · 被引用次数：1 · 研究领域：Medicine

Background Cuproptosis, a metal-ion-dependent form of regulated cell death induced by copper overload, is emerging as a potential mechanism in high-grade glioma (HGG). Despite its significance, the role of cuproptosis in predicting the prognostic and therapeutic response in HGG remains poorly understood. Methods We performed unsupervised clustering to stratify patients with HGG in the Chinese Glioma Genome Atlas (CGGA) according to the expression of 14 cuproptosis-related genes (CRGs) and validated in The Cancer Genome Atlas (TCGA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to explore the biological processes and pathways involved within distinct groups. We constructed the CupScore model to predict the responsiveness to immune checkpoint inhibitors (ICIs) therapy and chemotherapy in patients with HGG. Additionally, in vivo and in vitro experiments were performed to investigate the potential biological function of CDKN2A in HGG. Results We identified two cuproptosis-related molecular subgroups with significantly different survival probabilities. Patients with HGG in cluster 1 were characterized as immune-desert phenotype with higher CupScore and lower expression of MHC complex, interferons, chemokines, interleukins, and immune checkpoints. In contrast, cluster 2 showed an immune-inflamed signature. We screened PI-103 as the most promising candidate for patients with higher CupScore and confirmed its experimental evidence and cl...