Molecular and Clinical Characterization of a Novel Prognostic and Immunologic Biomarker GPSM3 in Low-Grade Gliomas

<b>Background:</b> as the most common malignancy of the central nervous system, low-grade glioma (LGG) patients suffered a poor prognosis. Tumor microenvironment, especially immune components, plays an important role in the progression of tumors. Thus, it is critical to explore the key i...

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Autores principales: Ming Wang, Jiaoying Jia, Yan Cui, Yong Peng, Yugang Jiang
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:0c2d481f95d648779df4b4da2eabcccb2021-11-25T16:59:08ZMolecular and Clinical Characterization of a Novel Prognostic and Immunologic Biomarker GPSM3 in Low-Grade Gliomas10.3390/brainsci111115292076-3425https://doaj.org/article/0c2d481f95d648779df4b4da2eabcccb2021-11-01T00:00:00Zhttps://www.mdpi.com/2076-3425/11/11/1529https://doaj.org/toc/2076-3425<b>Background:</b> as the most common malignancy of the central nervous system, low-grade glioma (LGG) patients suffered a poor prognosis. Tumor microenvironment, especially immune components, plays an important role in the progression of tumors. Thus, it is critical to explore the key immune-related genes, a comprehensive understanding of the TME in LGG helps us find novel cancer biomarkers and therapeutic targets. <b>Methods:</b> the GPSM3 expression level and the correlations between clinical characteristics and GPSM3 levels were analyzed with the data from CGGA and TCGA dataset. Univariate and multivariate cox regression model were built to predict the prognosis of LGG patients with multiple factors. Then the correlation between GPSM3 with immune cell infiltration was explored by ESTIMATE, CIBERSORT and TIMER2.0. At last, the correlation analyzed between GPSM3 expression and immune checkpoint related genes were also analyzed. <b>Results:</b> GPSM3 expression was overexpressed in LGG and negatively correlated to the GPSM3 DNA methylation. Univariate and multivariate Cox analysis demonstrated that GPSM3 expression was an independent prognostic factor in LGG patients. Functional characterization of GPSM3 revealed that it was associated with many immune processes to tumor cells. GPSM3 expression was positive related to the immune score, Stromal scores and ESTIMATE scores, but negative related to the Tumor purity. Immune features in the TME of GPSM3-high LGG group is characterized by a higher infiltrating of regulatory T cells, neutrophils, macrophages M2, and a lower proportion of monocytes than to the GPSM3-low group. Furthermore, GPSM3 expression exhibited significant correlations with the immune checkpoint-related genes, especially PD-1, PD-L1, PD-L2, CTLA4 and TIM3. <b>Conclusions:</b> these findings proved that GPSM3 could serve as a prognostic biomarker and potential immunotherapy target for LGG.Ming WangJiaoying JiaYan CuiYong PengYugang JiangMDPI AGarticlelow-grade gliomaTMEimmune cell infiltrationimmunotherapyNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENBrain Sciences, Vol 11, Iss 1529, p 1529 (2021)
institution DOAJ
collection DOAJ
language EN
topic low-grade glioma
TME
immune cell infiltration
immunotherapy
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
spellingShingle low-grade glioma
TME
immune cell infiltration
immunotherapy
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Ming Wang
Jiaoying Jia
Yan Cui
Yong Peng
Yugang Jiang
Molecular and Clinical Characterization of a Novel Prognostic and Immunologic Biomarker GPSM3 in Low-Grade Gliomas
description <b>Background:</b> as the most common malignancy of the central nervous system, low-grade glioma (LGG) patients suffered a poor prognosis. Tumor microenvironment, especially immune components, plays an important role in the progression of tumors. Thus, it is critical to explore the key immune-related genes, a comprehensive understanding of the TME in LGG helps us find novel cancer biomarkers and therapeutic targets. <b>Methods:</b> the GPSM3 expression level and the correlations between clinical characteristics and GPSM3 levels were analyzed with the data from CGGA and TCGA dataset. Univariate and multivariate cox regression model were built to predict the prognosis of LGG patients with multiple factors. Then the correlation between GPSM3 with immune cell infiltration was explored by ESTIMATE, CIBERSORT and TIMER2.0. At last, the correlation analyzed between GPSM3 expression and immune checkpoint related genes were also analyzed. <b>Results:</b> GPSM3 expression was overexpressed in LGG and negatively correlated to the GPSM3 DNA methylation. Univariate and multivariate Cox analysis demonstrated that GPSM3 expression was an independent prognostic factor in LGG patients. Functional characterization of GPSM3 revealed that it was associated with many immune processes to tumor cells. GPSM3 expression was positive related to the immune score, Stromal scores and ESTIMATE scores, but negative related to the Tumor purity. Immune features in the TME of GPSM3-high LGG group is characterized by a higher infiltrating of regulatory T cells, neutrophils, macrophages M2, and a lower proportion of monocytes than to the GPSM3-low group. Furthermore, GPSM3 expression exhibited significant correlations with the immune checkpoint-related genes, especially PD-1, PD-L1, PD-L2, CTLA4 and TIM3. <b>Conclusions:</b> these findings proved that GPSM3 could serve as a prognostic biomarker and potential immunotherapy target for LGG.
format article
author Ming Wang
Jiaoying Jia
Yan Cui
Yong Peng
Yugang Jiang
author_facet Ming Wang
Jiaoying Jia
Yan Cui
Yong Peng
Yugang Jiang
author_sort Ming Wang
title Molecular and Clinical Characterization of a Novel Prognostic and Immunologic Biomarker GPSM3 in Low-Grade Gliomas
title_short Molecular and Clinical Characterization of a Novel Prognostic and Immunologic Biomarker GPSM3 in Low-Grade Gliomas
title_full Molecular and Clinical Characterization of a Novel Prognostic and Immunologic Biomarker GPSM3 in Low-Grade Gliomas
title_fullStr Molecular and Clinical Characterization of a Novel Prognostic and Immunologic Biomarker GPSM3 in Low-Grade Gliomas
title_full_unstemmed Molecular and Clinical Characterization of a Novel Prognostic and Immunologic Biomarker GPSM3 in Low-Grade Gliomas
title_sort molecular and clinical characterization of a novel prognostic and immunologic biomarker gpsm3 in low-grade gliomas
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/0c2d481f95d648779df4b4da2eabcccb
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AT yancui molecularandclinicalcharacterizationofanovelprognosticandimmunologicbiomarkergpsm3inlowgradegliomas
AT yongpeng molecularandclinicalcharacterizationofanovelprognosticandimmunologicbiomarkergpsm3inlowgradegliomas
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