Targeting copper death genotyping associated gene RARRES2 suppresses glioblastoma progression and macrophages infiltration

作者：Tao Yan, Yang He, Yun Meng, Huadong Li, Qing Jiang, Junsi Liu, Caixia Xu, Yanpeng Xue, Jiayi Xu, Yan Song, Xiaojie Chu, Lijuan Wang, Xin Chen, Fengyuan Che · 发表于：Cancer Cell International · 年份：2023 · DOI：10.1186/s12935-023-02950-6 · 被引用次数：13 · 研究领域：Ferroptosis and cancer prognosis、Trace Elements in Health、Cancer Immunotherapy and Biomarkers

BACKGROUND: Copper homeostasis is associated with malignant biological behavior in various tumors. The excessive accumulation of copper can induce tumor death, which is named cuproptosis, and it is also closely related to tumor progression and the formation of the immune microenvironment. However, the associations of cuproptosis with glioblastoma (GBM) prognosis and microenvironment construction are poorly understood. METHOD: First, TCGA and GEO (GSE83300, GSE74187) merged datasets were used to analyze the association of cuproptosis-related genes (CRGs) with GBM. Then, we performed cluster analysis of CRGs in GBM from the GEO (GSE83300, GSE74187) and TCGA merged datasets. Subsequently, the prognostic risk model was constructed by least absolute shrinkage and selection operator (LASSO) according to gene expression features in CRG clusters. Next, we performed a series of in-depth analyses, including tumor mutational burden (TMB) analysis, cluster analysis, and GBM IDH status prediction. Finally, RARRES2 was identified as a target gene for GBM treatment, especially IDH wild-type GBM. In addition, we further analyzed the correlation of CRG clusters and RARRES2 expression with the GBM immune microenvironment by ESTIMATE and CIBERSORT analyses. In vitro experiments were conducted to demonstrate that targeting RARRES2 inhibits glioblastoma progression and macrophage infiltration, particularly IDH wild-type GBM. RESULTS: In the present study, we demonstrated that the CRG cluster was ...