Glioblastoma (GBM) is the most invasive type of glioma and is difficult to treat. Diverse programmed cell death (PCD) patterns have a significant association with tumor initiation and progression. A novel prognostic model based on PCD genes may serve as an effective tool to predict the prognosis of GBM. The study incorporated 11 PCD patterns, namely apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, entotic cell death, netotic cell death, parthanatos, lysosome-dependent cell death, autophagy-dependent cell death, alkaliptosis, and oxeiptosis, to develop the model. To construct and validate the model, both bulk and single-cell transcriptome data, along with corresponding clinical data from GBM cases, were obtained from the TCGA-GBM, REMBRANDT, CGGA, and GSE162631 datasets. A cell death-related signature containing 14 genes was constructed with the TCGA-GBM cohort and validated in the REMBRANDT and CGGA datasets. GBM patients with a higher cell death index (CDI) were significantly associated with poorer survival outcomes. Two separate clusters associated with clinical outcomes emerged from unsupervised analysis. A multivariate Cox regression analysis was conducted to examine the association of CDI with clinical characteristics, and a prognostic nomogram was developed. Drug sensitivity analysis revealed high-CDI GBM patients might be resistant to carmustine while sensitive to 5-fluorouracil. Less abundance of natural killer cells was found in GBM cases with high CDI and bulk transcriptome data. A cell death-related prognostic model that could predict the prognosis of GBM patients with good performance was established, which could discriminate between the prognosis and drug sensitivity of GBM.

胶质母细胞瘤（GBM）是最具侵袭性的胶质瘤类型，且难以治疗。不同的程序性细胞死亡（PCD）模式与肿瘤的发生和进展具有显着相关性。基于PCD基因的新型预后模型可能作为预测GBM预后的有效工具。该研究纳入了 11 种 PCD 模式，即细胞凋亡、坏死性凋亡、细胞焦亡、铁死亡、铜死亡、内入细胞死亡、网状细胞死亡、parthanatos、溶酶体依赖性细胞死亡、自噬依赖性细胞死亡、碱死亡和氧化死亡，以开发该模型。为了构建和验证模型，从 TCGA-GBM、REMBRANDT、CGGA 和 GSE162631 数据集中获得了批量和单细胞转录组数据以及 GBM 病例的相应临床数据。使用 TCGA-GBM 队列构建了包含 14 个基因的细胞死亡相关特征，并在 REMBRANDT 和 CGGA 数据集中进行了验证。细胞死亡指数 (CDI) 较高的 GBM 患者与较差的生存结果显着相关。无监督分析中出现了与临床结果相关的两个独立的集群。进行多变量 Cox 回归分析以检查 CDI 与临床特征的关联，并开发了预后列线图。药物敏感性分析显示，高 CDI GBM 患者可能对卡莫司汀耐药，而对 5-氟尿嘧啶敏感。在具有高 CDI 和大量转录组数据的 GBM 病例中发现自然杀伤细胞丰度较低。建立了可以预测表现良好的GBM患者预后的细胞死亡相关预后模型，可以区分GBM的预后和药物敏感性。