N7-methylguanosin regulators-mediated methylation modification patterns and characterization of the immune microenvironment in lower-grade glioma
Abstract N7-methylguanosine (m7G) modification signature has recently emerged as a crucial regulator of tumor progression and treatment in cancer. However, there is limited information available on the genomic profile of lower-grade gliomas (LGGs) related to m7G methylation modification genes’ funct...
Main Authors: | , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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BMC
2023-03-01
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Series: | European Journal of Medical Research |
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Online Access: | https://doi.org/10.1186/s40001-023-01108-4 |
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author | Aierpati Maimaiti Zhaohai Feng Yanwen Liu Mirzat Turhon Zhihao Xie Yilimire Baihetiyaer Xixian Wang Maimaitijiang Kasimu Lei Jiang Yongxin Wang Zengliang Wang Yinan Pei |
author_facet | Aierpati Maimaiti Zhaohai Feng Yanwen Liu Mirzat Turhon Zhihao Xie Yilimire Baihetiyaer Xixian Wang Maimaitijiang Kasimu Lei Jiang Yongxin Wang Zengliang Wang Yinan Pei |
author_sort | Aierpati Maimaiti |
collection | DOAJ |
description | Abstract N7-methylguanosine (m7G) modification signature has recently emerged as a crucial regulator of tumor progression and treatment in cancer. However, there is limited information available on the genomic profile of lower-grade gliomas (LGGs) related to m7G methylation modification genes’ function in tumorigenesis and progression. In this study, we employed bioinformatics methods to characterize m7G modifications in individuals with LGG from The Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA). We used gene set enrichment analysis (GSEA), single sample GSEA (ssGSEA), CIBERSORT algorithm, ESTIMATE algorithm, and TIDE to evaluate the association between m7G modification patterns, tumor microenvironment (TME) cell infiltration properties, and immune infiltration markers. The m7G scoring scheme using principal component analysis (PCA) was employed to investigate the m7G modification patterns quantitatively. We examined the m7G modification hub genes' expression levels in normal samples, refractory epilepsy samples, and LGG samples using immunohistochemistry, western-blotting, and qRT-PCR. Our findings revealed that individuals with LGG could be categorized into two groups based on m7G scores (high and low) according to the properties of m7G. Moreover, we observed that high m7G score was associated with significant clinical benefit and prolonged survival duration in the anti-PD-1 cohort, while low m7G score was associated with improved prognostic outcomes and increased likelihood of complete or partial response in the anti-PD-L1 cohort. Different m7G subtypes also showed varying Tumor Mutational Burden (TMB) and immune profiles and might have distinct responses to immunotherapy. Furthermore, we identified five potential genetic markers that were highly correlated with the m7G score signature index. These findings provide insight into the features and classification associated with m7G methylation modifications and may aid in improving the clinical outcome of LGG. |
first_indexed | 2024-03-08T12:39:21Z |
format | Article |
id | doaj.art-598739584be54a97be5901bd1a7b1c6e |
institution | Directory Open Access Journal |
issn | 2047-783X |
language | English |
last_indexed | 2024-03-08T12:39:21Z |
publishDate | 2023-03-01 |
publisher | BMC |
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series | European Journal of Medical Research |
spelling | doaj.art-598739584be54a97be5901bd1a7b1c6e2024-01-21T12:14:54ZengBMCEuropean Journal of Medical Research2047-783X2023-03-0128112210.1186/s40001-023-01108-4N7-methylguanosin regulators-mediated methylation modification patterns and characterization of the immune microenvironment in lower-grade gliomaAierpati Maimaiti0Zhaohai Feng1Yanwen Liu2Mirzat Turhon3Zhihao Xie4Yilimire Baihetiyaer5Xixian Wang6Maimaitijiang Kasimu7Lei Jiang8Yongxin Wang9Zengliang Wang10Yinan Pei11Department of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical UniversityDepartment of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical UniversityDepartment of Medical Laboratory, Xinjiang Production and Construction Corps HospitalDepartment of Neurointerventional Surgery, Beijing Neurosurgical Institute, Capital Medical UniversityThe Second Hospital of Jilin UniversityDepartment of Neurology, The First Affiliated Hospital of Xinjiang Medical UniversityDepartment of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical UniversityDepartment of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical UniversityDepartment of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical UniversityDepartment of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical UniversityDepartment of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical UniversityDepartment of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical UniversityAbstract N7-methylguanosine (m7G) modification signature has recently emerged as a crucial regulator of tumor progression and treatment in cancer. However, there is limited information available on the genomic profile of lower-grade gliomas (LGGs) related to m7G methylation modification genes’ function in tumorigenesis and progression. In this study, we employed bioinformatics methods to characterize m7G modifications in individuals with LGG from The Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA). We used gene set enrichment analysis (GSEA), single sample GSEA (ssGSEA), CIBERSORT algorithm, ESTIMATE algorithm, and TIDE to evaluate the association between m7G modification patterns, tumor microenvironment (TME) cell infiltration properties, and immune infiltration markers. The m7G scoring scheme using principal component analysis (PCA) was employed to investigate the m7G modification patterns quantitatively. We examined the m7G modification hub genes' expression levels in normal samples, refractory epilepsy samples, and LGG samples using immunohistochemistry, western-blotting, and qRT-PCR. Our findings revealed that individuals with LGG could be categorized into two groups based on m7G scores (high and low) according to the properties of m7G. Moreover, we observed that high m7G score was associated with significant clinical benefit and prolonged survival duration in the anti-PD-1 cohort, while low m7G score was associated with improved prognostic outcomes and increased likelihood of complete or partial response in the anti-PD-L1 cohort. Different m7G subtypes also showed varying Tumor Mutational Burden (TMB) and immune profiles and might have distinct responses to immunotherapy. Furthermore, we identified five potential genetic markers that were highly correlated with the m7G score signature index. These findings provide insight into the features and classification associated with m7G methylation modifications and may aid in improving the clinical outcome of LGG.https://doi.org/10.1186/s40001-023-01108-4N7-methylguanosineAnti-PD-1/L1 immunotherapyLower-grade gliomaPrognostic signatureTumor microenvironment |
spellingShingle | Aierpati Maimaiti Zhaohai Feng Yanwen Liu Mirzat Turhon Zhihao Xie Yilimire Baihetiyaer Xixian Wang Maimaitijiang Kasimu Lei Jiang Yongxin Wang Zengliang Wang Yinan Pei N7-methylguanosin regulators-mediated methylation modification patterns and characterization of the immune microenvironment in lower-grade glioma European Journal of Medical Research N7-methylguanosine Anti-PD-1/L1 immunotherapy Lower-grade glioma Prognostic signature Tumor microenvironment |
title | N7-methylguanosin regulators-mediated methylation modification patterns and characterization of the immune microenvironment in lower-grade glioma |
title_full | N7-methylguanosin regulators-mediated methylation modification patterns and characterization of the immune microenvironment in lower-grade glioma |
title_fullStr | N7-methylguanosin regulators-mediated methylation modification patterns and characterization of the immune microenvironment in lower-grade glioma |
title_full_unstemmed | N7-methylguanosin regulators-mediated methylation modification patterns and characterization of the immune microenvironment in lower-grade glioma |
title_short | N7-methylguanosin regulators-mediated methylation modification patterns and characterization of the immune microenvironment in lower-grade glioma |
title_sort | n7 methylguanosin regulators mediated methylation modification patterns and characterization of the immune microenvironment in lower grade glioma |
topic | N7-methylguanosine Anti-PD-1/L1 immunotherapy Lower-grade glioma Prognostic signature Tumor microenvironment |
url | https://doi.org/10.1186/s40001-023-01108-4 |
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