DataSheet_1_Development and validation of cuproptosis-associated prognostic signatures in WHO 2/3 glioma.zip

WHO 2/3 glioma is a common intracranial tumor that seriously affects the quality of life and survival time of patients. Previous studies have shown that the tricarboxylic acid (TCA) cycle is closely related to the occurrence and development of glioma, while recent studies have shown that cuproptosis, a novel programmed death pathway, is closely related to the inhibition of the TCA cycle. In our study, eight of ten cuproptosis-related genes (CRGs) were found to be differentially expressed between normal and WHO 2/3 glioma tissues. Through the LASSO algorithm, the cuproptosis-associated risk signatures (CARSs) were constructed, which can effectively predict the prognosis of WHO 2/3 glioma patients and are closely related to clinicopathological features. We analyzed the relationship between risk score and immune cell infiltration through Xcell, ssGSEA, TIMER database, and immune checkpoint molecules. In addition, the relationship between risk score and chemotherapeutic drug sensitivity was also investigated. The prognosis-related independent risk factors FDX1 and CDKN2A identified from CARSs are considered potential prognostic biomarkers for WHO 2/3 glioma. The clinical prognosis model based on cuproptosis is expected to provide an effective reference for the diagnosis and treatment of clinical WHO 2/3 glioma patients.

WHO Ⅱ/Ⅲ级胶质瘤是一类常见的颅内肿瘤，严重影响患者的生活质量与生存时长。既往研究表明，三羧酸（TCA）循环与胶质瘤的发生发展密切相关；而近期研究发现，新型程序性死亡通路铜死亡（cuproptosis）与TCA循环抑制存在紧密关联。本研究中，我们发现10个铜死亡相关基因（CRGs）中有8个，在正常组织与WHO Ⅱ/Ⅲ级胶质瘤组织中存在差异表达。通过最小绝对收缩和选择算子（LASSO）算法，我们构建了铜死亡相关风险特征（CARSs），该特征可有效预测WHO Ⅱ/Ⅲ级胶质瘤患者的预后，且与临床病理特征密切相关。我们借助Xcell、ssGSEA、TIMER数据库以及免疫检查点分子，分析了风险评分与免疫细胞浸润之间的关联。此外，本研究还探讨了风险评分与化疗药物敏感性的关系。从CARSs中筛选出的预后相关独立风险因素FDX1与CDKN2A，被认为是WHO Ⅱ/Ⅲ级胶质瘤的潜在预后生物标志物。基于铜死亡的临床预后模型，有望为临床WHO Ⅱ/Ⅲ级胶质瘤患者的诊疗提供有效参考。