Cancer Center Union Hospital Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Comput Intell Neurosci. 2022 Apr 15;2022:9046507. doi: 10.1155/2022/9046507. eCollection 2022.
Pyroptosis is a programmed cell death mediated by gasdermins (GSDMs). The prognostic value of pyroptosis-related genes in different tumor types has been gradually demonstrated recently. However, the prognostic impact of GSDMs expression in glioma remains unclear. Here, we present a comprehensive bioinformatic analysis of gasdermin family member gene expression, producing a prognostic model for glioma and creating a competing endogenous RNA (ceRNA) network. The mRNA expression profiles and clinical information of glioma patients were downloaded from TCGA and CGGA. A risk score based on the gasdermin family was constructed in the TCGA cohort and validated in CGGA. The Jurkat cell was used to verify the relationship between pyroptosis and activation-induced cell death (AICD). We identify a significant association between the expression of GSDMD and GSDME and the glioma stage. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was used to construct a prognostic gene model based on the four prognostic gasdermin family genes (GSDMC, GSDMD, GSDME, and PJVK). This model was able to predict the overall survival of glioma patients with high accuracy. We show that gasdermin family genes are expressed primarily by immune cells, endothelial cells, and neuronal cells in the tumor microenvironment, rather than by malignant tumor cells. T cells were significantly activated in high-risk patients; however, the activation-induced cell death (AICD) pathway was also significantly activated, suggesting widespread expiration of cytotoxic T lymphocytes (CTLs), facilitating tumor progression. We also identify the lncRNA/miR-296-5p/GSDMD regulatory axis as an important player in glioma progression. We have conducted a comprehensive bioinformatic analysis identifying the importance of gasdermin family members in glioma; a prognostic algorithm containing four genes was constructed.
细胞焦亡是由gasdermins（GSDMs）介导的程序性细胞死亡。最近，gasdermin 相关基因在不同肿瘤类型中的预后价值逐渐得到证实。然而，GSDMs 表达在神经胶质瘤中的预后影响尚不清楚。在这里，我们对 GSDM 家族成员基因表达进行了全面的生物信息学分析，为神经胶质瘤生成了一个预后模型，并构建了一个竞争性内源性 RNA（ceRNA）网络。从 TCGA 和 CGGA 下载了神经胶质瘤患者的 mRNA 表达谱和临床信息。在 TCGA 队列中构建了基于 GSDM 家族的风险评分，并在 CGGA 中进行了验证。使用 Jurkat 细胞验证了细胞焦亡与激活诱导的细胞死亡（AICD）之间的关系。我们发现 GSDMD 和 GSDME 的表达与神经胶质瘤分期显著相关。使用最小绝对收缩和选择算子（LASSO）Cox 回归分析基于四个预后 GSDM 家族基因（GSDMC、GSDMD、GSDME 和 PJVK）构建了预后基因模型。该模型能够准确预测神经胶质瘤患者的总生存期。我们表明，GSDM 家族基因主要在肿瘤微环境中的免疫细胞、内皮细胞和神经元细胞中表达，而不是在恶性肿瘤细胞中表达。在高危患者中 T 细胞明显被激活；然而，激活诱导的细胞死亡（AICD）途径也明显被激活，这表明细胞毒性 T 淋巴细胞（CTL）广泛衰竭，促进了肿瘤的进展。我们还确定了 lncRNA/miR-296-5p/GSDMD 调控轴作为神经胶质瘤进展的一个重要参与者。我们进行了全面的生物信息学分析，确定了 GSDM 家族成员在神经胶质瘤中的重要性；构建了包含四个基因的预后算法。
