{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:54:27Z","timestamp":1790351667158,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,13]],"date-time":"2020-05-13T00:00:00Z","timestamp":1589328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["1R01 CA176203-01A1"],"award-info":[{"award-number":["1R01 CA176203-01A1"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Science Center of Poland","award":["2018\/29\/B\/NZ1\/01016"],"award-info":[{"award-number":["2018\/29\/B\/NZ1\/01016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Malignant brain tumor\u2014glioblastoma 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\u2019s 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\u2019 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\u2019 outcomes by driving tumor cell adaptation to metabolic stress and immune escape.<\/jats:p>","DOI":"10.3390\/cancers12051213","type":"journal-article","created":{"date-parts":[[2020,5,14]],"date-time":"2020-05-14T02:55:41Z","timestamp":1589424941000},"page":"1213","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Hypoxic Roadmap of Glioblastoma\u2014Learning about Directions and Distances in the Brain Tumor Environment"],"prefix":"10.3390","volume":"12","author":[{"given":"Agnieszka","family":"Bronisz","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Harvey Cushing Neuro-Oncology Laboratories, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4212-221X","authenticated-orcid":false,"given":"El\u017cbieta","family":"Sali\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Antonio","family":"Chiocca","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Harvey Cushing Neuro-Oncology Laboratories, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Godlewski","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Harvey Cushing Neuro-Oncology Laboratories, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N. Engl. J. 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