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...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-05-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/5/1213 |
| _version_ | 1797568167369768960 |
|---|---|
| author | Agnieszka Bronisz Elżbieta Salińska E. Antonio Chiocca Jakub Godlewski |
| author_facet | Agnieszka Bronisz Elżbieta Salińska E. Antonio Chiocca Jakub Godlewski |
| author_sort | Agnieszka Bronisz |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T19:52:34Z |
| format | Article |
| id | doaj.art-67beade1f43443689cb9efdf9b5d0993 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T19:52:34Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-67beade1f43443689cb9efdf9b5d09932023-11-20T00:14:58ZengMDPI AGCancers2072-66942020-05-01125121310.3390/cancers12051213Hypoxic Roadmap of Glioblastoma—Learning about Directions and Distances in the Brain Tumor EnvironmentAgnieszka Bronisz0Elżbieta Salińska1E. Antonio Chiocca2Jakub Godlewski3Department of Neurosurgery, Harvey Cushing Neuro-Oncology Laboratories, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106 Warsaw, PolandDepartment of Neurosurgery, Harvey Cushing Neuro-Oncology Laboratories, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Neurosurgery, Harvey Cushing Neuro-Oncology Laboratories, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USAMalignant 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.https://www.mdpi.com/2072-6694/12/5/1213glioblastomahypoxiatranscriptomeautophagyimmune response |
| spellingShingle | Agnieszka Bronisz Elżbieta Salińska E. Antonio Chiocca Jakub Godlewski Hypoxic Roadmap of Glioblastoma—Learning about Directions and Distances in the Brain Tumor Environment Cancers glioblastoma hypoxia transcriptome autophagy immune response |
| 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 | glioblastoma hypoxia transcriptome autophagy immune response |
| url | https://www.mdpi.com/2072-6694/12/5/1213 |
| work_keys_str_mv | AT agnieszkabronisz hypoxicroadmapofglioblastomalearningaboutdirectionsanddistancesinthebraintumorenvironment AT elzbietasalinska hypoxicroadmapofglioblastomalearningaboutdirectionsanddistancesinthebraintumorenvironment AT eantoniochiocca hypoxicroadmapofglioblastomalearningaboutdirectionsanddistancesinthebraintumorenvironment AT jakubgodlewski hypoxicroadmapofglioblastomalearningaboutdirectionsanddistancesinthebraintumorenvironment |