Zheng Xiaohong, Pan Zhangchi, Chen Lina, Wang Can, Li Wenbin
Department of Medical Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Front Immunol. 2025 Jul 21;16:1617036. doi: 10.3389/fimmu.2025.1617036. eCollection 2025.
Glioblastoma (GBM) is a highly malignant brain tumor with a poor prognosis. The WHO Classification of Tumors of the Central Nervous System (WHO CNS5) reclassified GBM in 2021. Pyroptosis, as an inflammatory form of programmed cell death, could regulate tumor cell proliferation, invasion, and metastasis. However, the role of pyroptosis in the newly defined GBM and its correlation with immunity have not yet been elucidated.
According to the 2021 WHO CNS5, a total of 209 newly defined GBM samples from The Cancer Genome Atlas (TCGA) cohort were included for analysis. The Chinese Glioma Genome Atlas (CGGA) cohort was used as the validation set. The prognosis model was built by Least Absolute Shrinkage and Selection Operator (LASSO) Cox analysis. The nomogram was conducted to confirm the prognostic value of risk score. ESTIMATE, CIBERSORTx, and ImmuCellAI were used to investigate immune infiltration. Quantitative real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed to validate PLCG1 and NOD2 genes in the prognostic model.
The risk score model including the two genes was built. The experimental results verified that elevated NOD2 expression and reduced PLCG1 expression in GBM represent poor prognosis with a higher risk. This risk score model could predict the survival rates of patients with GBM with medium to high accuracy. The benefit of chemotherapy or radiotherapy was greater in the high-risk group than in the low-risk group. Moreover, the high-risk group had stronger immune activity and poorer immunotherapy response.
In summary, our study provided strong evidence for the prognosis and clinical management of the newly defined GBM from bioinformatics and experimental analysis. Furthermore, our findings provided a foundation for future research targeting pyroptosis and its immune microenvironment to improve GBM prognosis.
胶质母细胞瘤（GBM）是一种预后较差的高度恶性脑肿瘤。世界卫生组织中枢神经系统肿瘤分类（WHO CNS5）于2021年对GBM进行了重新分类。细胞焦亡作为程序性细胞死亡的一种炎症形式，可调节肿瘤细胞的增殖、侵袭和转移。然而，细胞焦亡在新定义的GBM中的作用及其与免疫的相关性尚未阐明。
根据2021年WHO CNS5，纳入了来自癌症基因组图谱（TCGA）队列的209个新定义的GBM样本进行分析。中国胶质瘤基因组图谱（CGGA）队列用作验证集。通过最小绝对收缩和选择算子（LASSO）Cox分析建立预后模型。绘制列线图以确认风险评分的预后价值。使用ESTIMATE、CIBERSORTx和ImmuCellAI研究免疫浸润。进行定量实时聚合酶链反应（RT-qPCR）和免疫组织化学以验证预后模型中的PLCG1和NOD2基因。
构建了包含这两个基因的风险评分模型。实验结果证实，GBM中NOD2表达升高和PLCG1表达降低代表预后不良且风险较高。该风险评分模型能够以中等至高的准确率预测GBM患者的生存率。高危组化疗或放疗的获益大于低危组。此外，高危组具有更强的免疫活性和更差的免疫治疗反应。
总之，我们的研究从生物信息学和实验分析方面为新定义的GBM的预后和临床管理提供了有力证据。此外，我们的研究结果为未来针对细胞焦亡及其免疫微环境改善GBM预后的研究奠定了基础。
