Department of Neurology, Heyuan Hospital of Guangdong Provincial People's Hospital, Heyuan People's Hospital, Heyuan 517000, China.
Department of Anesthesia, Zhongshan Hospital of Chinese Medicine, Zhongshan 528400, China.
Oxid Med Cell Longev. 2023 Jan 31;2023:4256116. doi: 10.1155/2023/4256116. eCollection 2023.
Gliomas are highly invasive and aggressive tumors having the highest incidence rate of brain cancer. Identifying effective prognostic and potential therapeutic targets is necessitated. The relationship of pyroptosis, a form of programmed cellular death, with gliomas remains elusive. We constructed and validated a prognostic model for gliomas using pyroptosis-related genes. Differentially expressed pyroptosis-related genes were screened using the "limma" package. Based on LASSO-Cox regression, nine significant genes including CASP1, CASP3, CASP6, IL32, MKI67, MYD88, PRTN3, NOS1, and VIM were employed to construct a prognostic model in the TCGA cohort; the results were validated in the CGGA cohort. According to the median risk score, the patients were classified into two risk groups, namely, high- and low-risk groups. Patients at high risk had worse prognoses relative to those at low risk evidenced by the Kaplan-Meier curve analysis. The two groups exhibited differences in immune cell infiltration and TMB scores, with high immune checkpoint levels, TMB scores, and immune cell infiltration levels in the high-risk group. KEGG and GO analyses suggested enrichment in immune-related pathways. Furthermore, we found that the genes in our signature strongly correlated with oxidative stress-related pathways and the subgroups exhibited different ssGSEA scores. Some small molecules targeted the genes in the model, and we verified their drug sensitivities between the risk groups. The scRNA-seq dataset, GSE138794, was processed using the "Seurat" package to assess the level of risk gene expression in specific cell types. Finally, the MYD88 level was lowered in the U87 glioma cell line using si-RNA constructs. Cellular proliferation was impaired, and fewer pyroptosis-related cytokines were released upon exposure to LPS. In summary, we built a pyroptosis-related gene model that accurately classified glioma patients into high- and low-risk groups. The findings suggest that the signature may be an effective prognostic predictive tool for gliomas.
神经胶质瘤是高度侵袭性和侵袭性肿瘤，是脑癌发病率最高的肿瘤。因此，有必要确定有效的预后和潜在的治疗靶点。细胞程序性死亡的一种形式——细胞焦亡与神经胶质瘤之间的关系仍不清楚。我们使用与细胞焦亡相关的基因构建并验证了神经胶质瘤的预后模型。使用“limma”包筛选差异表达的与细胞焦亡相关的基因。基于 LASSO-Cox 回归，我们在 TCGA 队列中使用 9 个显著基因（包括 CASP1、CASP3、CASP6、IL32、MKI67、MYD88、PRTN3、NOS1 和 VIM）构建了一个预后模型；并在 CGGA 队列中验证了该模型。根据中位风险评分，患者被分为高风险和低风险两组。通过 Kaplan-Meier 曲线分析，高风险组患者的预后明显差于低风险组患者。两组患者的免疫细胞浸润和 TMB 评分存在差异，高风险组的免疫检查点水平、TMB 评分和免疫细胞浸润水平较高。KEGG 和 GO 分析表明，该模型富集在免疫相关通路中。此外，我们发现模型中的基因与氧化应激相关通路密切相关，并且亚组之间的 ssGSEA 评分存在差异。一些小分子靶向模型中的基因，我们验证了它们在风险组之间的药物敏感性。使用“Seurat”包处理 scRNA-seq 数据集 GSE138794，以评估特定细胞类型中风险基因表达的水平。最后，我们使用 si-RNA 构建体降低 U87 神经胶质瘤细胞系中的 MYD88 水平。细胞增殖受损，LPS 暴露后释放的细胞焦亡相关细胞因子减少。总之，我们构建了一个基于与细胞焦亡相关的基因模型，该模型可以准确地将神经胶质瘤患者分为高风险和低风险组。这些发现表明，该标志物可能是神经胶质瘤的一种有效的预后预测工具。
