期刊
BIOMOLECULES
卷 13, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/biom13060904
关键词
glioma; GSDMD; prognosis; tumor microenvironment; immune cell infiltration
A recent study revealed that gasdermin D (GSDMD) is upregulated in glioma tissues and is associated with shorter overall survival in patients. Upregulation of GSDMD is also linked to higher tumor mutation burden and PD-1/PD-L1 expression. Furthermore, GSDMD is positively correlated with immune infiltrates, including macrophages and cancer-associated fibroblasts, in an immunosuppressive microenvironment. Knockdown of GSDMD inhibits glioma proliferation, migration, and growth.
Background: Understanding the molecular mechanisms driving oncogenic processes in glioma is important in order to develop efficient treatments. Recent studies have proposed gasdermin D (GSDMD) as a newly discovered pyroptosis executive protein associated with tumorigenesis. However, the precise effect of GSDMD on glioma progression remains unknown. Methods: The expression levels of GSDMD in 931 glioma and 1157 normal control tissues were collected. A series of bioinformatic approaches and in vivo and in vitro experiments were used to investigate the roles and mechanisms of GDSMD in glioma. Results: Significant upregulation of GSDMD was detected in glioma tissues compared to normal brain tissues. Patients with glioma and higher GSDMD levels had shorter overall survival, and the Cox regression analysis revealed that GSDMD was an independent risk factor. In addition, upregulation of GSDMD was associated with higher tumor mutation burden and PD-1/PD-L1 expression. Immune infiltration and single-cell analyses indicated that GSDMD was positively associated with an immunosuppressive microenvironment with more infiltrated macrophages and cancer-associated fibroblasts. Furthermore, the in vitro and in vivo experiments revealed that GSDMD knockdown inhibited glioma proliferation, migration, and growth in vivo. Conclusion: Our analyses revealed a relatively comprehensive understanding of the oncogenic role of GSDMD in glioma. GSDMD is a promising prognostic biomarker and a potential target for glioma treatment.
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