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Molecular profile reveals immune-associated markers of medulloblastoma for different subtypes

Medulloblastoma, a common pediatric malignant tumor, has been recognized to have four molecular subgroups [wingless (WNT), sonic hedgehog (SHH), group 3, group 4], which are defined by the characteristic gene transcriptomic and DNA methylomic profiles, and has distinct clinical features within each...

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Autores principales: Chen, Jinyi, Kang, Zhuang, Li, Shenglan, Wang, Can, Zheng, Xiaohong, Cai, Zehao, Pan, Lexin, Chen, Feng, Li, Wenbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9367478/
https://www.ncbi.nlm.nih.gov/pubmed/35967388
http://dx.doi.org/10.3389/fimmu.2022.911260
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author Chen, Jinyi
Kang, Zhuang
Li, Shenglan
Wang, Can
Zheng, Xiaohong
Cai, Zehao
Pan, Lexin
Chen, Feng
Li, Wenbin
author_facet Chen, Jinyi
Kang, Zhuang
Li, Shenglan
Wang, Can
Zheng, Xiaohong
Cai, Zehao
Pan, Lexin
Chen, Feng
Li, Wenbin
author_sort Chen, Jinyi
collection PubMed
description Medulloblastoma, a common pediatric malignant tumor, has been recognized to have four molecular subgroups [wingless (WNT), sonic hedgehog (SHH), group 3, group 4], which are defined by the characteristic gene transcriptomic and DNA methylomic profiles, and has distinct clinical features within each subgroup. The tumor immune microenvironment is integral in tumor initiation and progression and might be associated with therapeutic responses. However, to date, the immune infiltrative landscape of medulloblastoma has not yet been elucidated. Thus, we proposed MethylCIBERSORT to estimate the degree of immune cell infiltration and weighted correlation network analysis (WGCNA) to find modules of highly correlated genes. Synthesizing the hub genes in the protein–protein interaction (PPI) network and modules of the co-expression network, we identify three candidate biomarkers [GRB2-associated-binding protein 1 (GAB1), Abelson 1 (ABL1), and CXC motif chemokine receptor type 4 (CXCR4)] via the molecular profiles of medulloblastoma. Given this, we investigated the correlation between these three immune hub genes and immune checkpoint blockade response and the potential of drug prediction further. In addition, this study demonstrated a higher presence of endothelial cells and infiltrating immune cells in Group 3 tumor bulk. The above results will be conducive to better comprehending the immune-related pathogenesis and treatment of medulloblastoma.
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spelling pubmed-93674782022-08-12 Molecular profile reveals immune-associated markers of medulloblastoma for different subtypes Chen, Jinyi Kang, Zhuang Li, Shenglan Wang, Can Zheng, Xiaohong Cai, Zehao Pan, Lexin Chen, Feng Li, Wenbin Front Immunol Immunology Medulloblastoma, a common pediatric malignant tumor, has been recognized to have four molecular subgroups [wingless (WNT), sonic hedgehog (SHH), group 3, group 4], which are defined by the characteristic gene transcriptomic and DNA methylomic profiles, and has distinct clinical features within each subgroup. The tumor immune microenvironment is integral in tumor initiation and progression and might be associated with therapeutic responses. However, to date, the immune infiltrative landscape of medulloblastoma has not yet been elucidated. Thus, we proposed MethylCIBERSORT to estimate the degree of immune cell infiltration and weighted correlation network analysis (WGCNA) to find modules of highly correlated genes. Synthesizing the hub genes in the protein–protein interaction (PPI) network and modules of the co-expression network, we identify three candidate biomarkers [GRB2-associated-binding protein 1 (GAB1), Abelson 1 (ABL1), and CXC motif chemokine receptor type 4 (CXCR4)] via the molecular profiles of medulloblastoma. Given this, we investigated the correlation between these three immune hub genes and immune checkpoint blockade response and the potential of drug prediction further. In addition, this study demonstrated a higher presence of endothelial cells and infiltrating immune cells in Group 3 tumor bulk. The above results will be conducive to better comprehending the immune-related pathogenesis and treatment of medulloblastoma. Frontiers Media S.A. 2022-07-28 /pmc/articles/PMC9367478/ /pubmed/35967388 http://dx.doi.org/10.3389/fimmu.2022.911260 Text en Copyright © 2022 Chen, Kang, Li, Wang, Zheng, Cai, Pan, Chen and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Chen, Jinyi
Kang, Zhuang
Li, Shenglan
Wang, Can
Zheng, Xiaohong
Cai, Zehao
Pan, Lexin
Chen, Feng
Li, Wenbin
Molecular profile reveals immune-associated markers of medulloblastoma for different subtypes
title Molecular profile reveals immune-associated markers of medulloblastoma for different subtypes
title_full Molecular profile reveals immune-associated markers of medulloblastoma for different subtypes
title_fullStr Molecular profile reveals immune-associated markers of medulloblastoma for different subtypes
title_full_unstemmed Molecular profile reveals immune-associated markers of medulloblastoma for different subtypes
title_short Molecular profile reveals immune-associated markers of medulloblastoma for different subtypes
title_sort molecular profile reveals immune-associated markers of medulloblastoma for different subtypes
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9367478/
https://www.ncbi.nlm.nih.gov/pubmed/35967388
http://dx.doi.org/10.3389/fimmu.2022.911260
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