Gasdermin D Is a Novel Prognostic Biomarker and Relates to TMZ Response in Glioblastoma

The gasdermin (GSDM) family act as executioners during pyroptosis. However, its expression and biological role in glioma remain to be determined. This study carried out gene expression from six public datasets. Westerns blots and immunohistochemistry (IHC) staining were employed to examine GSDM expr...

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Autores principales:	Junhui Liu, Lun Gao, Xiaonan Zhu, Rongxin Geng, Xiang Tao, Haitao Xu, Zhibiao Chen
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	gasdermin family pyroptosis glioma prognosis immune temozolomide Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/1de8f0f0561a46b6b02d3bceac598ad1
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spelling	oai:doaj.org-article:1de8f0f0561a46b6b02d3bceac598ad12021-11-25T17:01:42ZGasdermin D Is a Novel Prognostic Biomarker and Relates to TMZ Response in Glioblastoma10.3390/cancers132256202072-6694https://doaj.org/article/1de8f0f0561a46b6b02d3bceac598ad12021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5620https://doaj.org/toc/2072-6694The gasdermin (GSDM) family act as executioners during pyroptosis. However, its expression and biological role in glioma remain to be determined. This study carried out gene expression from six public datasets. Westerns blots and immunohistochemistry (IHC) staining were employed to examine GSDM expression in glioma in an in-house cohort. Kaplan–Meier and Cox regression analyses were performed to evaluate the prognostic role of GSDMs in glioma. Association between gene expression and immune infiltration was assessed by IHC and immunofluorescence (IF) staining of tissue sections. TMZ-induced pyroptosis was assessed by observation of morphological changes, WB and ELISA detection. Only GSDMD expression was upregulated in glioma compared with nontumor brain tissues both in the public datasets and in-house cohort. High GSDMD expression was significantly associated with WHO grade IV, IDH 1/2 wild-type and mesenchymal subtypes. Besides, high GSDMD expression was associated with shorter overall survival and could be used as an independent risk factor for poor outcomes in LGG and GBM. GO enrichment analysis and IHC validation revealed that GSDMD expression might participate in regulating macrophage infiltration and polarization. TMZ treatment induced the pyroptosis in GBM cells and GSDMD expression increased with after treating with TMZ in a time-dependent manner. Moreover, knocking down GSDMD obviously decreased IL-1β expression and reduced TMZ-induced pyroptosis in in vitro. GSDMD was a novel prognostic biomarker, as well as TMZ-treatment response marker in glioma.Junhui LiuLun GaoXiaonan ZhuRongxin GengXiang TaoHaitao XuZhibiao ChenMDPI AGarticlegasdermin familypyroptosisgliomaprognosisimmunetemozolomideNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5620, p 5620 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	gasdermin family pyroptosis glioma prognosis immune temozolomide Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	gasdermin family pyroptosis glioma prognosis immune temozolomide Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Junhui Liu Lun Gao Xiaonan Zhu Rongxin Geng Xiang Tao Haitao Xu Zhibiao Chen Gasdermin D Is a Novel Prognostic Biomarker and Relates to TMZ Response in Glioblastoma
description	The gasdermin (GSDM) family act as executioners during pyroptosis. However, its expression and biological role in glioma remain to be determined. This study carried out gene expression from six public datasets. Westerns blots and immunohistochemistry (IHC) staining were employed to examine GSDM expression in glioma in an in-house cohort. Kaplan–Meier and Cox regression analyses were performed to evaluate the prognostic role of GSDMs in glioma. Association between gene expression and immune infiltration was assessed by IHC and immunofluorescence (IF) staining of tissue sections. TMZ-induced pyroptosis was assessed by observation of morphological changes, WB and ELISA detection. Only GSDMD expression was upregulated in glioma compared with nontumor brain tissues both in the public datasets and in-house cohort. High GSDMD expression was significantly associated with WHO grade IV, IDH 1/2 wild-type and mesenchymal subtypes. Besides, high GSDMD expression was associated with shorter overall survival and could be used as an independent risk factor for poor outcomes in LGG and GBM. GO enrichment analysis and IHC validation revealed that GSDMD expression might participate in regulating macrophage infiltration and polarization. TMZ treatment induced the pyroptosis in GBM cells and GSDMD expression increased with after treating with TMZ in a time-dependent manner. Moreover, knocking down GSDMD obviously decreased IL-1β expression and reduced TMZ-induced pyroptosis in in vitro. GSDMD was a novel prognostic biomarker, as well as TMZ-treatment response marker in glioma.
format	article
author	Junhui Liu Lun Gao Xiaonan Zhu Rongxin Geng Xiang Tao Haitao Xu Zhibiao Chen
author_facet	Junhui Liu Lun Gao Xiaonan Zhu Rongxin Geng Xiang Tao Haitao Xu Zhibiao Chen
author_sort	Junhui Liu
title	Gasdermin D Is a Novel Prognostic Biomarker and Relates to TMZ Response in Glioblastoma
title_short	Gasdermin D Is a Novel Prognostic Biomarker and Relates to TMZ Response in Glioblastoma
title_full	Gasdermin D Is a Novel Prognostic Biomarker and Relates to TMZ Response in Glioblastoma
title_fullStr	Gasdermin D Is a Novel Prognostic Biomarker and Relates to TMZ Response in Glioblastoma
title_full_unstemmed	Gasdermin D Is a Novel Prognostic Biomarker and Relates to TMZ Response in Glioblastoma
title_sort	gasdermin d is a novel prognostic biomarker and relates to tmz response in glioblastoma
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1de8f0f0561a46b6b02d3bceac598ad1
work_keys_str_mv	AT junhuiliu gasdermindisanovelprognosticbiomarkerandrelatestotmzresponseinglioblastoma AT lungao gasdermindisanovelprognosticbiomarkerandrelatestotmzresponseinglioblastoma AT xiaonanzhu gasdermindisanovelprognosticbiomarkerandrelatestotmzresponseinglioblastoma AT rongxingeng gasdermindisanovelprognosticbiomarkerandrelatestotmzresponseinglioblastoma AT xiangtao gasdermindisanovelprognosticbiomarkerandrelatestotmzresponseinglioblastoma AT haitaoxu gasdermindisanovelprognosticbiomarkerandrelatestotmzresponseinglioblastoma AT zhibiaochen gasdermindisanovelprognosticbiomarkerandrelatestotmzresponseinglioblastoma
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Gasdermin D Is a Novel Prognostic Biomarker and Relates to TMZ Response in Glioblastoma

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