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Hypoxic Roadmap of Glioblastoma—Learning about Directions and Distances in the Brain Tumor Environment

Malignant brain tumor—glioblastoma is not only difficult to treat but also hard to study and model. One of the reasons for these is their heterogeneity, i.e., individual tumors consisting of cancer cells that are unlike each other. Such diverse cells can thrive due to the simultaneous co-evolution o...

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Autores principales: Bronisz, Agnieszka, Salińska, Elżbieta, Chiocca, E. Antonio, Godlewski, Jakub
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281616/
https://www.ncbi.nlm.nih.gov/pubmed/32413951
http://dx.doi.org/10.3390/cancers12051213
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author Bronisz, Agnieszka
Salińska, Elżbieta
Chiocca, E. Antonio
Godlewski, Jakub
author_facet Bronisz, Agnieszka
Salińska, Elżbieta
Chiocca, E. Antonio
Godlewski, Jakub
author_sort Bronisz, Agnieszka
collection PubMed
description Malignant brain tumor—glioblastoma is not only difficult to treat but also hard to study and model. One of the reasons for these is their heterogeneity, i.e., individual tumors consisting of cancer cells that are unlike each other. Such diverse cells can thrive due to the simultaneous co-evolution of anatomic niches and adaption into zones with distorted homeostasis of oxygen. It dampens cytotoxic and immune therapies as the response depends on the cellular composition and its adaptation to hypoxia. We explored what transcriptome reposition strategies are used by cells in the different areas of the tumor. We created the hypoxic map by differential expression analysis between hypoxic and cellular features using RNA sequencing data cross-referenced with the tumor’s anatomic features (Ivy Glioblastoma Atlas Project). The molecular functions of genes differentially expressed in the hypoxic regions were analyzed by a systematic review of the gene ontology analysis. To put a hypoxic niche signature into a clinical context, we associated the model with patients’ survival datasets (The Cancer Genome Atlas). The most unique class of genes in the hypoxic area of the tumor was associated with the process of autophagy. Both hypoxic and cellular anatomic features were enriched in immune response genes whose, along with autophagy cluster genes, had the power to predict glioblastoma patient survival. Our analysis revealed that transcriptome responsive to hypoxia predicted worse patients’ outcomes by driving tumor cell adaptation to metabolic stress and immune escape.
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spelling pubmed-72816162020-06-17 Hypoxic Roadmap of Glioblastoma—Learning about Directions and Distances in the Brain Tumor Environment Bronisz, Agnieszka Salińska, Elżbieta Chiocca, E. Antonio Godlewski, Jakub Cancers (Basel) Article Malignant brain tumor—glioblastoma is not only difficult to treat but also hard to study and model. One of the reasons for these is their heterogeneity, i.e., individual tumors consisting of cancer cells that are unlike each other. Such diverse cells can thrive due to the simultaneous co-evolution of anatomic niches and adaption into zones with distorted homeostasis of oxygen. It dampens cytotoxic and immune therapies as the response depends on the cellular composition and its adaptation to hypoxia. We explored what transcriptome reposition strategies are used by cells in the different areas of the tumor. We created the hypoxic map by differential expression analysis between hypoxic and cellular features using RNA sequencing data cross-referenced with the tumor’s anatomic features (Ivy Glioblastoma Atlas Project). The molecular functions of genes differentially expressed in the hypoxic regions were analyzed by a systematic review of the gene ontology analysis. To put a hypoxic niche signature into a clinical context, we associated the model with patients’ survival datasets (The Cancer Genome Atlas). The most unique class of genes in the hypoxic area of the tumor was associated with the process of autophagy. Both hypoxic and cellular anatomic features were enriched in immune response genes whose, along with autophagy cluster genes, had the power to predict glioblastoma patient survival. Our analysis revealed that transcriptome responsive to hypoxia predicted worse patients’ outcomes by driving tumor cell adaptation to metabolic stress and immune escape. MDPI 2020-05-13 /pmc/articles/PMC7281616/ /pubmed/32413951 http://dx.doi.org/10.3390/cancers12051213 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bronisz, Agnieszka
Salińska, Elżbieta
Chiocca, E. Antonio
Godlewski, Jakub
Hypoxic Roadmap of Glioblastoma—Learning about Directions and Distances in the Brain Tumor Environment
title Hypoxic Roadmap of Glioblastoma—Learning about Directions and Distances in the Brain Tumor Environment
title_full Hypoxic Roadmap of Glioblastoma—Learning about Directions and Distances in the Brain Tumor Environment
title_fullStr Hypoxic Roadmap of Glioblastoma—Learning about Directions and Distances in the Brain Tumor Environment
title_full_unstemmed Hypoxic Roadmap of Glioblastoma—Learning about Directions and Distances in the Brain Tumor Environment
title_short Hypoxic Roadmap of Glioblastoma—Learning about Directions and Distances in the Brain Tumor Environment
title_sort hypoxic roadmap of glioblastoma—learning about directions and distances in the brain tumor environment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281616/
https://www.ncbi.nlm.nih.gov/pubmed/32413951
http://dx.doi.org/10.3390/cancers12051213
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