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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7281616 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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