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Pyroptosis: a novel signature to predict prognosis and immunotherapy response in gliomas

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Abstract

Gliomas are the most common primary brain tumors and are highly malignant with a poor prognosis. Pyroptosis, an inflammatory form of programmed cell death, promotes the inflammatory cell death of cancer. Studies have demonstrated that pyroptosis can promote the inflammatory cell death (ICD) of cancer, thus affecting the prognosis of cancer patients. Therefore, genes that control pyroptosis could be a promising candidate bio-indicator in tumor therapy. The function of pyroptosis-related genes (PRGs) in gliomas was investigated based on the Chinese Glioma Genome Atlas (CGGA), the Cancer Genome Atlas (TCGA) and the Repository of Molecular Brain Neoplasia Data (Rembrandt) databases. In this study, using the non-negative matrix factorization (NMF) clustering method, 26 PRGs from the RNA sequencing data were divided into two subgroups. The LASSO and Cox regression was used to develop a 4-gene (BAX, Caspase-4, Caspase-8, PLCG1) risk signature, and all glioma patients in the CGGA, TCGA and Rembrandt cohorts were divided into low- and high-risk groups. The results demonstrate that the gene risk signature related to clinical features can be used as an independent prognostic indicator in glioma patients. Moreover, the high-risk subtype had rich immune infiltration and high expression of immune checkpoint genes in the tumor immune microenvironment (TIME). The analysis of the Submap algorithm shows that patients in the high-risk group could benefit more from anti-PD1 treatment. The risk characteristics associated with pyroptosis proposed in this study play an essential role in TIME and can potentially predict the prognosis and immunotherapeutic response of glioma patients.

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Data availability

The datasets used in this study are available in CGGA, TCGA and Rembrandt databases.

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Acknowledgements

We thank the contributions of CGGA, TCGA and Rembrandt database for providing free access to online data.

Funding

This work was supported by Finance science and technology project of hainan province (Grant No. ZDYF2022SHFZ088 and ZDYF2019129), the National Nature Science Foundation of China (Grant No. 82060456), the Innovative Research Project of Hainan Graduate Students (Grant No. Qhyb2021-58) and project supported by Hainan Province Clinical Medical Center.

Author information

Author notes

  1. Guiying He, Zhimin Chen and Shenghua Zhuo are co-first authors.

Authors and Affiliations

  1. Department of Neurology, Shenzhen Nanshan People’s Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518052, Guangdong, China

    Guiying He & Chunshui Yang

  2. State Key Laboratory of Oncogenes and Related Genes, School of Medicine, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, 200127, China

    Zhimin Chen & Weijie Hao

  3. Department of Neurosurgery, The First Affiliated Hospital of Hainan Medical University, Haikou, 570102, Hainan, China

    Shenghua Zhuo & Kun Yang

  4. Department of Ultrasound, Fudan University Shanghai Cancer Center, Shanghai, 200433, China

    Jingzhi Tang

Authors
  1. Guiying He
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  2. Zhimin Chen
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  3. Shenghua Zhuo
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  4. Jingzhi Tang
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  5. Weijie Hao
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  6. Kun Yang
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  7. Chunshui Yang
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Contributions

CY and KY conceived and designed the study and drafted the manuscript. GH, ZC and SZ performed data analysis and manuscript writing. JT and WH revised the manuscript. All authors reviewed the manuscript. GH, ZC and SZ contributed equally to this work.

Corresponding authors

Correspondence to Kun Yang or Chunshui Yang.

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Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethics approval

The Medical Ethics Committee of the First Affiliated Hospital of Hainan Medical University reviewed and approved the acquisition of tumor specimens (2022 (Scientific Research L) No. (145)).

Consent to participate

The data processing met the CGGA, TCGA and Rembrandt database publication guidelines.

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Not applicable.

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He, G., Chen, Z., Zhuo, S. et al. Pyroptosis: a novel signature to predict prognosis and immunotherapy response in gliomas. Human Cell 35, 1976–1992 (2022). https://doi.org/10.1007/s13577-022-00791-5

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