ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1617036
This article is part of the Research TopicMetabolism and Tumor Microenvironment Nexus in Neuro-OncologyView all articles
The pyroptosis-related gene signature predicts prognosis and reveals immune microenvironment infiltration in reclassified glioblastoma based on 2021 WHO classification
Provisionally accepted
- 1Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- 2Beijing Tiantan Hospital, Capital Medical University, Beijing, Beijing Municipality, China
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Background: Glioblastoma (GBM) is a highly malignant brain tumor with poor prognosis. The WHO Classification of Tumors of the Central Nervous System 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 newly defined GBM and their correlations with immunity have not yet been elucidated. Method: According to 2021 WHO CNS5, A total of 209 newly defined GBM samples from TCGA cohort were included for analysis. The CGGA cohort was used as the validation set. The prognosis model was built by LASSO Cox analysis. The nomogram was conducted to confirm the prognostic value of risk score. ESTIMATE, CIBERSORTx, and ImmuCellAI were used to investigate the immune infiltration. The RT-qPCR and immunohistochemistry were performed to validate PLCG1 and NOD2 genes in the prognostic model. Results: The risk score model included two genes was built. The experimental results verified that elevated NOD2 expression and reduced PLCG1 expression in GBM represent poor prognosis with higher risk. This risk score model could predict the survival rates of GBM patients with medium-to-high accuracy. The benefit of chemotherapy or radiotherapy was greater in the high-risk group than in the low-risk group. What’s more, the high-risk group had stronger immune activity and poorer immunotherapy response. Conclusions: In summary, our study provided strong evidence for the prognosis and clinical management of newly defined GBM from bioinformatics and experimental analysis. What’s more, our findings provided a foundation for future research targeting pyroptosis and its immune microenvironment to improve GBM prognosis.
Keywords: ：pyroptosis, Glioblastoma, Immune infiltration, clinical therapy, Prognostic model
Received: 23 Apr 2025; Accepted: 18 Jun 2025.
Copyright: © 2025 Zheng, Pan, Chen, Wang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Can Wang, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, Beijing Municipality, China
Wenbin Li, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, Beijing Municipality, China
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