Alterations in Astrocyte Subpopulations in Glioma and Identification of Cuproptosis-Related Genes Using Single-Cell RNA Sequencing

Purpose: Mitochondrial metabolism is essential for energy production and the survival of brain cells, particularly in astrocytes.Cuproptosis is a newly identified form of programmed cell death that occurs due to the disruption of mitochondrial metabolism caused by excessive copper toxicity.However, the relationship between cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) and the prognosis of gliomas remains unclear.Patients and Methods: In this study, we utilized 32,293 cells obtained from three in-house single-cell RNA sequencing (scRNAseq) datasets, along with 6,148 cells acquired from the Chinese Glioma Genome Atlas (CGGA) involving 14 glioma patients, to identify and validate the TME of gliomas.Results: Based on an analysis of 32,293 single cells, we investigated intra-tumor heterogeneity, intercellular communication, and astrocyte differentiation trajectories in gliomas.Our findings revealed that the TGFβ signaling pathway exhibited a higher relative strength in astrocyte subpopulations.Additionally, we identified a novel three-gene signature (CDKN2A, SOX2, and MPC1) was identified for prognostic prediction.Furthermore, glioma patients with a high-risk score demonstrated poorer overall survival (OS) compared to those with a low-risk score in both training and testing datasets (P training set < 0.001; P test set = 0.037). Conclusion:Our study revealed the prognostic value of the CRGs in astrocytes exhibiting tumor immunosuppressive characteristics in glioma.We established a novel three-gene prognostic model that offers new insights into the prognosis and treatment strategies for gliomas.