背景：胶质瘤是一种高度异质性的疾病，给预后预测带来了挑战。通过燃气素（GSDM）介导的程序性细胞死亡，热死亡区别于细胞肿胀和炎症因子的释放。热死亡在多种肿瘤细胞（包括胶质瘤）中发生。然而，与胶质瘤预后相关的热死亡相关基因（PRGs）的价值仍有待进一步澄清。 方法：本研究从TCGA和CGGA数据库获取了胶质瘤患者的mRNA表达谱和临床数据，并从分子签名数据库和GeneCards获得了118个PRGs。然后，进行共识聚类分析来聚类胶质瘤患者。使用最小绝对收缩和选择算子（LASSO）Cox回归模型建立多基因签名。通过基因敲除和Western印迹检验实现与热死亡相关基因GSDMD的功能验证。此外，通过“gsva” R包分析了两个不同风险组之间的免疫浸润状态。 结果：我们的结果表明，在TCGA队列中，大多数PRGs（82.2％）在低级别胶质瘤（LGG）和胶质母细胞瘤（GBM）之间有差异表达。在单变量Cox回归分析中，八十三个PRGs与总生存率（OS）相关。建立了一个五基因签名来将患者分为两个风险组。与低风险组的患者相比，高风险组的患者OS明显较短（p <0.001）。此外，我们发现高风险组显示出更高的免疫细胞浸润得分和免疫相关功能。风险评分是OS的独立预测因子（HR> 1，p <0.001）。此外，GSDMD的敲除降低了IL-1β和裂解的caspase-1的表达。 结论：我们的研究构建了一个新的PRGs标志，可用于预测胶质瘤患者的预后。针对热死亡可能成为胶质瘤的潜在治疗策略。版权所有©2023年Sun，Wang，Zhong，Yu，Xuan，Xu，Song，Yang，Wang，Liu，Meng和Cai。

Background: Glioma is a highly heterogeneous disease, causing the prognostic prediction a challenge. Pyroptosis, a programmed cell death mediated by gasdermin (GSDM), is characterized by cell swelling and the release of inflammatory factors. Pyroptosis occurs in several types of tumor cells, including gliomas. However, the value of pyroptosis-related genes (PRGs) in the prognosis of glioma remains to be further clarified. Methods: In this study, mRNA expression profiles and clinical data of glioma patients were acquired from TCGA and CGGA databases, and one hundred and eighteen PRGs were obtained from the Molecular Signatures Database and GeneCards. Then, consensus clustering analysis was performed to cluster glioma patients. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to establish a polygenic signature. Functional verification of the pyroptosis-related gene GSDMD was achieved by gene knockdown and western blotting. Moreover, the immune infiltration status between two different risk groups were analyzed through the "gsva" R package. Results: Our results demonstrated that the majority of PRGs (82.2%) were differentially expressed between lower-grade gliomas (LGG) and glioblastoma (GBM) in the TCGA cohort. In univariate Cox regression analysis, eighty-three PRGs were shown to be associated with overall survival (OS). A five-gene signature was constructed to divide patients into two risk groups. Compared with patients in the low-risk group, patients in the high-risk group had obviously shorter OS (p < 0.001). Also, we found that the high-risk group showed a higher infiltrating score of immune cells and immune-related functions. Risk score was an independent predictor of OS (HR > 1, p < 0.001). Furthermore, knockdown of GSDMD decreased the expression of IL-1β and cleaved caspase-1. Conclusion: Our study constructed a new PRGs signature, which can be used to predict the prognosis of glioma patients. Targeting pyroptosis might serve as a potential therapeutic strategy for glioma.Copyright © 2023 Sun, Wang, Zhong, Yu, Xuan, Xu, Song, Yang, Wang, Liu, Meng and Cai.