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...

Full description

Bibliographic Details
Main Authors: Aierpati Maimaiti, Zhaohai Feng, Yanwen Liu, Mirzat Turhon, Zhihao Xie, Yilimire Baihetiyaer, Xixian Wang, Maimaitijiang Kasimu, Lei Jiang, Yongxin Wang, Zengliang Wang, Yinan Pei
Format: Article
Language:English
Published: BMC 2023-03-01
Series:European Journal of Medical Research
Subjects:
Online Access:https://doi.org/10.1186/s40001-023-01108-4
_version_ 1797350058970054656
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
record_format Article
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
work_keys_str_mv AT aierpatimaimaiti n7methylguanosinregulatorsmediatedmethylationmodificationpatternsandcharacterizationoftheimmunemicroenvironmentinlowergradeglioma
AT zhaohaifeng n7methylguanosinregulatorsmediatedmethylationmodificationpatternsandcharacterizationoftheimmunemicroenvironmentinlowergradeglioma
AT yanwenliu n7methylguanosinregulatorsmediatedmethylationmodificationpatternsandcharacterizationoftheimmunemicroenvironmentinlowergradeglioma
AT mirzatturhon n7methylguanosinregulatorsmediatedmethylationmodificationpatternsandcharacterizationoftheimmunemicroenvironmentinlowergradeglioma
AT zhihaoxie n7methylguanosinregulatorsmediatedmethylationmodificationpatternsandcharacterizationoftheimmunemicroenvironmentinlowergradeglioma
AT yilimirebaihetiyaer n7methylguanosinregulatorsmediatedmethylationmodificationpatternsandcharacterizationoftheimmunemicroenvironmentinlowergradeglioma
AT xixianwang n7methylguanosinregulatorsmediatedmethylationmodificationpatternsandcharacterizationoftheimmunemicroenvironmentinlowergradeglioma
AT maimaitijiangkasimu n7methylguanosinregulatorsmediatedmethylationmodificationpatternsandcharacterizationoftheimmunemicroenvironmentinlowergradeglioma
AT leijiang n7methylguanosinregulatorsmediatedmethylationmodificationpatternsandcharacterizationoftheimmunemicroenvironmentinlowergradeglioma
AT yongxinwang n7methylguanosinregulatorsmediatedmethylationmodificationpatternsandcharacterizationoftheimmunemicroenvironmentinlowergradeglioma
AT zengliangwang n7methylguanosinregulatorsmediatedmethylationmodificationpatternsandcharacterizationoftheimmunemicroenvironmentinlowergradeglioma
AT yinanpei n7methylguanosinregulatorsmediatedmethylationmodificationpatternsandcharacterizationoftheimmunemicroenvironmentinlowergradeglioma