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世界卫生组织2/3级胶质瘤中铜死亡相关预后特征的开发与验证

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

作者信息

Ye Zhang, Zhang Shenqi, Cai Jiayang, Ye Liguo, Gao Lun, Wang Yixuan, Tong Shiao, Sun Qian, Wu Yu, Xiong Xiaoxing, Chen Qianxue

机构信息

Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, China.

Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.

出版信息

Front Oncol. 2022 Aug 18;12:967159. doi: 10.3389/fonc.2022.967159. eCollection 2022.

Abstract

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.

摘要

世界卫生组织(WHO)2/3级胶质瘤是一种常见的颅内肿瘤,严重影响患者的生活质量和生存时间。以往研究表明,三羧酸(TCA)循环与胶质瘤的发生发展密切相关,而最近的研究表明,铜死亡作为一种新的程序性死亡途径,与TCA循环的抑制密切相关。在我们的研究中,发现十个铜死亡相关基因(CRGs)中有八个在正常组织和WHO 2/3级胶质瘤组织之间存在差异表达。通过LASSO算法构建了铜死亡相关风险特征(CARSs),其能够有效预测WHO 2/3级胶质瘤患者的预后,且与临床病理特征密切相关。我们通过Xcell、单样本基因集富集分析(ssGSEA)、肿瘤免疫评估资源(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系。此外,还研究了风险评分与化疗药物敏感性之间的关系。从CARSs中鉴定出的与预后相关的独立风险因素FDX1和CDKN2A被认为是WHO 2/3级胶质瘤潜在的预后生物标志物。基于铜死亡的临床预后模型有望为临床WHO 2/3级胶质瘤患者的诊断和治疗提供有效的参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcef/9434124/eea200f33a66/fonc-12-967159-g001.jpg

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