Zhang Zihao, Wang Bingcheng, Xu Xiaoqin, Xin Tao
Department of Surgery, Shandong Provincial Hospital, Shandong University, Jinan, China.
Department of Neurosurgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.
Front Genet. 2022 Oct 25;13:1036460. doi: 10.3389/fgene.2022.1036460. eCollection 2022.
Cuproptosis is the most recently discovered type of regulated cell death and is mediated by copper ions. Studies show that cuproptosis plays a significant role in cancer development and progression. Lower-grade gliomas (LGGs) are slow-growing brain tumors. The majority of LGGs progress to high-grade glioma, which makes it difficult to predict the prognosis. However, the prognostic value of cuproptosis-related genes (CRGs) in LGG needs to be further explored. mRNA expression profiles and clinical data of LGG patients were collected from public sources for this study. Univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) Cox regression model were used to build a multigene signature that could divide patients into different risk groups. The differences in clinical pathological characteristics, immune infiltration characteristics, and mutation status were evaluated in risk subgroups. In addition, drug sensitivity and immune checkpoint scores were estimated in risk subgroups to provide LGG patients with precision medication. We found that all CRGs were differentially expressed in LGG and normal tissues. Patients were divided into high- and low-risk groups based on the risk score of the CRG signature. Patients in the high-risk group had a considerably lower overall survival rate than those in the low-risk group. According to functional analysis, pathways related to the immune system were enriched, and the immune state differed across the two risk groups. Immune characteristic analysis showed that the immune cell proportion and immune scores were different in the different groups. High-risk group was characterized by low sensitivity to chemotherapy but high sensitivity to immune checkpoint inhibitors. The current study revealed that the novel CRG signature was related to the prognosis, clinicopathological features, immune characteristics, and treatment perference of LGG.
铜死亡是最近发现的一种受调控的细胞死亡类型，由铜离子介导。研究表明，铜死亡在癌症的发生和发展中起重要作用。低级别胶质瘤（LGGs）是生长缓慢的脑肿瘤。大多数LGGs会进展为高级别胶质瘤，这使得预后难以预测。然而，铜死亡相关基因（CRGs）在LGG中的预后价值有待进一步探索。本研究从公共来源收集了LGG患者的mRNA表达谱和临床数据。采用单因素Cox回归分析和最小绝对收缩和选择算子（LASSO）Cox回归模型构建多基因特征，将患者分为不同风险组。评估风险亚组中临床病理特征、免疫浸润特征和突变状态的差异。此外，还估计了风险亚组中的药物敏感性和免疫检查点评分，为LGG患者提供精准用药。我们发现所有CRGs在LGG和正常组织中均有差异表达。根据CRG特征的风险评分将患者分为高风险组和低风险组。高风险组患者的总生存率明显低于低风险组。功能分析表明，与免疫系统相关的通路富集，两个风险组的免疫状态不同。免疫特征分析表明，不同组的免疫细胞比例和免疫评分不同。高风险组的特点是对化疗敏感性低，但对免疫检查点抑制剂敏感性高。当前研究表明，新的CRG特征与LGG的预后、临床病理特征、免疫特征和治疗偏好有关。
