坏死性凋亡相关基因特征的综合分析可预测低级别胶质瘤的临床结果、免疫状态和药物敏感性。
Integrated analysis of necroptosis related gene signature to predict clinical outcomes, immune status and drug sensitivity in lower grade Glioma.
发表日期:2024 Jan 15
作者:
Xiqi Hu, Yanan Ma, Ying Xia, Bo Liu
来源:
Cell Death & Disease
摘要:
低级别胶质瘤(LGG)的治疗是目前颅内肿瘤治疗中最具挑战性的难题。坏死性凋亡是一种与肿瘤进展密切相关的程序性细胞死亡,然而坏死性凋亡相关基因在LGG中的作用尚未得到很好的阐明。利用在线数据库获取基因表达和临床信息。经过基因差异表达分析,构建了基于预后差异表达坏死性凋亡相关基因(DENG)的风险评分模型来预测 LGG 患者的预后。然后用 Kaplan-Meier 生存曲线评估风险评分模型的有效性。然后对风险评分模型中包含的预后DENG进行基因表达分析、功能富集分析、共识聚类分析和单细胞测序分析。最后,我们研究了LGG肿瘤微环境中的风险评分和免疫浸润以及不同风险组LGG患者的药物敏感性的相关性。基于七个预后DENG构建了生存风险评分模型,在预测LGG患者的预后方面表现出了令人满意的性能。 LGG患者。根据功能富集分析,这七个DENG可能通过多种免疫和代谢途径在LGG肿瘤发生中发挥调节作用。根据 7 个 DENG 的表达情况,LGG 患者可分为具有不同预后和临床病理特征的两类。单细胞测序分析表明,DENG 特征在 LGG 的各种类型细胞中差异表达,可能在肿瘤发生中发挥重要作用。此外,药物敏感性分析表明七基因特征可以指导 LGG 患者的临床用药。我们的研究开发了可靠的坏死性凋亡相关特征来预测 LGG 患者的预后。该基因特征还可能有助于估计 LGG 患者的免疫状态和抗癌药物敏感性。我们的研究结果可能为增强我们对 LGG 坏死性凋亡的理解铺平道路。© 2023 作者。
The treatment of lower grade gliomas (LGG) is currently the most challenging dilemma in the management of intracranial tumors. Necroptosis is a type of programmed cell death that is closely associated with tumor progression, However, the role of necroptosis related genes in LGG is not yet well elucidated.Online databases were used to obtain gene expression and clinical information. After gene differential expression analysis, a risk score model based on prognostic differentially expressed necroptosis-related genes (DENGs) were constructed to predict prognosis for LGG patients. The validity of the risk score model was then assessed with Kaplan-Meier survival curve. The prognostic DENGs included in the risk score model were then subjected to gene expression analysis, functional enrichment analysis, consensus clustering analysis, and single cell sequencing analysis. Finally, we investigated the correlation of the risk score and immune infiltration in LGG tumor microenvironment and drug sensitivity for LGG patients in different risk groups.A survival risk score model was constructed based on seven prognostic DENGs, which demonstrated satisfactory performance in predicting the prognosis of LGG patients. According to functional enrichment analyses, these seven DENGs may play a regulatory role in LGG tumorigenesis through several immune and metabolic pathways. LGG patients could be categorized into two clusters with distinct prognosis and clinicopathologic characteristics based on the expression of seven DENGs. Single-cell sequencing analysis demonstrated that the DENG signature was differentially expressed in various types of cells in LGG and may play a vital role in oncogenesis. Additionally, drug sensitivity analysis suggested that the seven-gene signature could guide clinical medication for LGG patients.Our study developed a reliable necroptosis-related signature to predict the prognosis of LGG patients. This gene signature may also help estimate immune status and anti-cancer drug sensitivity in LGG patients. Our findings may pave the way to enhance our understanding of necroptosis in LGG.© 2023 The Authors.