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Immunological profiles of human oligodendrogliomas define two distinct molecular subtypes

BACKGROUND: Human oligodendroglioma presents as a heterogeneous disease, primarily characterized by the isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion. Therapy development for this tumor is hindered by incomplete knowledge of somatic driving alterations and suboptimal disease classif...

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Autores principales: Wu, Fan, Yin, Yi-Yun, Fan, Wen-Hua, Zhai, You, Yu, Ming-Chen, Wang, Di, Pan, Chang-Qing, Zhao, Zheng, Li, Guan-Zhang, Zhang, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9772571/
https://www.ncbi.nlm.nih.gov/pubmed/36525723
http://dx.doi.org/10.1016/j.ebiom.2022.104410
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author Wu, Fan
Yin, Yi-Yun
Fan, Wen-Hua
Zhai, You
Yu, Ming-Chen
Wang, Di
Pan, Chang-Qing
Zhao, Zheng
Li, Guan-Zhang
Zhang, Wei
author_facet Wu, Fan
Yin, Yi-Yun
Fan, Wen-Hua
Zhai, You
Yu, Ming-Chen
Wang, Di
Pan, Chang-Qing
Zhao, Zheng
Li, Guan-Zhang
Zhang, Wei
author_sort Wu, Fan
collection PubMed
description BACKGROUND: Human oligodendroglioma presents as a heterogeneous disease, primarily characterized by the isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion. Therapy development for this tumor is hindered by incomplete knowledge of somatic driving alterations and suboptimal disease classification. We herein aim to identify intrinsic molecular subtypes through integrated analysis of transcriptome, genome and methylome. METHODS: 137 oligodendroglioma patients from the Cancer Genome Atlas (TCGA) dataset were collected for unsupervised clustering analysis of immune gene expression profiles and comparative analysis of genome and methylome. Two independent datasets containing 218 patients were used for validation. FINDINGS: We identified and independently validated two reproducible subtypes associated with distinct molecular characteristics and clinical outcomes. The proliferative subtype, named Oligo1, was characterized by more tumors of CNS WHO grade 3, as well as worse prognosis compared to the Oligo2 subtype. Besides the clinicopathologic features, Oligo1 exhibited enrichment of cell proliferation, regulation of cell cycle and Wnt signaling pathways, and significantly altered genes, such as EGFR, NOTCH1 and MET. In contrast, Oligo2, with favorable outcome, presented increased activation of immune response and metabolic process. Higher T cell/APC co-inhibition and inhibitory checkpoint levels were observed in Oligo2 tumors. Finally, multivariable analysis revealed our classification was an independent prognostic factor in oligodendrogliomas, and the robustness of these molecular subgroups was verified in the validation cohorts. INTERPRETATION: This study provides further insights into patient stratification as well as presents opportunities for therapeutic development in human oligodendrogliomas. FUNDING: The funders are listed in the Acknowledgement.
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spelling pubmed-97725712022-12-23 Immunological profiles of human oligodendrogliomas define two distinct molecular subtypes Wu, Fan Yin, Yi-Yun Fan, Wen-Hua Zhai, You Yu, Ming-Chen Wang, Di Pan, Chang-Qing Zhao, Zheng Li, Guan-Zhang Zhang, Wei eBioMedicine Articles BACKGROUND: Human oligodendroglioma presents as a heterogeneous disease, primarily characterized by the isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion. Therapy development for this tumor is hindered by incomplete knowledge of somatic driving alterations and suboptimal disease classification. We herein aim to identify intrinsic molecular subtypes through integrated analysis of transcriptome, genome and methylome. METHODS: 137 oligodendroglioma patients from the Cancer Genome Atlas (TCGA) dataset were collected for unsupervised clustering analysis of immune gene expression profiles and comparative analysis of genome and methylome. Two independent datasets containing 218 patients were used for validation. FINDINGS: We identified and independently validated two reproducible subtypes associated with distinct molecular characteristics and clinical outcomes. The proliferative subtype, named Oligo1, was characterized by more tumors of CNS WHO grade 3, as well as worse prognosis compared to the Oligo2 subtype. Besides the clinicopathologic features, Oligo1 exhibited enrichment of cell proliferation, regulation of cell cycle and Wnt signaling pathways, and significantly altered genes, such as EGFR, NOTCH1 and MET. In contrast, Oligo2, with favorable outcome, presented increased activation of immune response and metabolic process. Higher T cell/APC co-inhibition and inhibitory checkpoint levels were observed in Oligo2 tumors. Finally, multivariable analysis revealed our classification was an independent prognostic factor in oligodendrogliomas, and the robustness of these molecular subgroups was verified in the validation cohorts. INTERPRETATION: This study provides further insights into patient stratification as well as presents opportunities for therapeutic development in human oligodendrogliomas. FUNDING: The funders are listed in the Acknowledgement. Elsevier 2022-12-14 /pmc/articles/PMC9772571/ /pubmed/36525723 http://dx.doi.org/10.1016/j.ebiom.2022.104410 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Articles
Wu, Fan
Yin, Yi-Yun
Fan, Wen-Hua
Zhai, You
Yu, Ming-Chen
Wang, Di
Pan, Chang-Qing
Zhao, Zheng
Li, Guan-Zhang
Zhang, Wei
Immunological profiles of human oligodendrogliomas define two distinct molecular subtypes
title Immunological profiles of human oligodendrogliomas define two distinct molecular subtypes
title_full Immunological profiles of human oligodendrogliomas define two distinct molecular subtypes
title_fullStr Immunological profiles of human oligodendrogliomas define two distinct molecular subtypes
title_full_unstemmed Immunological profiles of human oligodendrogliomas define two distinct molecular subtypes
title_short Immunological profiles of human oligodendrogliomas define two distinct molecular subtypes
title_sort immunological profiles of human oligodendrogliomas define two distinct molecular subtypes
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9772571/
https://www.ncbi.nlm.nih.gov/pubmed/36525723
http://dx.doi.org/10.1016/j.ebiom.2022.104410
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