Zhang Yan, Dai Xuehui, Li Zhanzhan
Department of Pathology, The Second Affiliated Hospital of Zhengzhou University Zhengzhou, Henan Province, China.
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University Zhengzhou, Henan Province, China.
Am J Transl Res. 2022 Nov 15;14(11):8085-8102. eCollection 2022.
Cuproptosis is a newly described form of cell death. However, nothing is known about the roles of cuproptosis regulators in glioma. First, we explored the characteristics of cuproptosis molecular subtypes and relevant tumor microenvironment (TME) immune cell infiltration patterns in glioma. Using unsupervised clustering analysis, we identified two cuproptosis subtypes and three gene clusters that exhibited different clinical characteristics and TME cell infiltration patterns. Then, we developed and validated a cuproptosis-related prognostic model for predicting the overall survival of glioma patients. We established a risk score tool based on a nomogram to assess the clinical applicability of the cuproptosis model. A high cuproptosis risk score with high immune cell infiltration level, tumor mutation burden, gene alterations, and immunity activation had an unfavorable overall survival. Next, we identified possible competing endogenous ribonucleic acid regulatory networks based on significantly differentially expressed genes between high-risk and low-risk groups and screened several candidate small molecular compounds that may improve chemotherapy. Data from IMvigor and GSE78200 showed that the cuproptosis score affected the prognosis of patients who received immunotherapy. Our study indicated that cuproptosis regulators are involved in TME immune infiltration and impact the clinical prognosis in glioma. It is necessary for clinical practice to develop different therapeutic strategies according to the different phenotypes associated with immune response. The present findings provide new insight for improving immunotherapy strategies and individualized treatment in glioma.
铜死亡是一种新描述的细胞死亡形式。然而，关于铜死亡调节因子在胶质瘤中的作用尚无任何了解。首先，我们探讨了胶质瘤中铜死亡分子亚型的特征以及相关肿瘤微环境（TME）免疫细胞浸润模式。通过无监督聚类分析，我们鉴定出两种铜死亡亚型和三个基因簇，它们表现出不同的临床特征和TME细胞浸润模式。然后，我们开发并验证了一种用于预测胶质瘤患者总生存期的铜死亡相关预后模型。我们基于列线图建立了一个风险评分工具，以评估铜死亡模型的临床适用性。高铜死亡风险评分且免疫细胞浸润水平高、肿瘤突变负担高、基因改变多以及免疫激活的患者总生存期较差。接下来，我们基于高风险组和低风险组之间显著差异表达的基因鉴定了可能的竞争性内源性核糖核酸调控网络，并筛选了几种可能改善化疗的候选小分子化合物。来自IMvigor和GSE78200的数据表明，铜死亡评分影响接受免疫治疗患者的预后。我们的研究表明，铜死亡调节因子参与TME免疫浸润并影响胶质瘤的临床预后。临床实践有必要根据与免疫反应相关的不同表型制定不同的治疗策略。本研究结果为改善胶质瘤的免疫治疗策略和个体化治疗提供了新的见解。
