{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T13:55:28Z","timestamp":1764251728422,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T00:00:00Z","timestamp":1627344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Involvement of the subventricular zone (SVZ) in glioblastoma is associated with poor prognosis and is associated with specific tumor-biological characteristics. The SVZ microenvironment can influence gene expression in glioblastoma cells in preclinical models. We aimed to investigate whether the SVZ microenvironment has any influence on intratumoral gene expression patterns in glioblastoma patients. Methods: The publicly available Ivy Glioblastoma database contains clinical, radiological and whole exome sequencing data from multiple regions from resected glioblastomas. SVZ involvement of the various tissue samples was evaluated on MRI scans. In tumors that contacted the SVZ, we performed gene expression analyses and gene set enrichment analyses to compare gene (set) expression in tumor regions within the SVZ to tumor regions outside the SVZ. We also compared these samples to glioblastomas that did not contact the SVZ. Results: Within glioblastomas that contacted the SVZ, tissue samples within the SVZ showed enrichment of gene sets involved in (epithelial-)mesenchymal transition, NF-\u03baB and STAT3 signaling, angiogenesis and hypoxia, compared to the samples outside of the SVZ region from the same tumors (p &lt; 0.05, FDR &lt; 0.25). Comparison of glioblastoma samples within the SVZ region to samples from tumors that did not contact the SVZ yielded similar results. In contrast, we observed no differences when comparing the samples outside of the SVZ from SVZ-contacting glioblastomas with samples from glioblastomas that did not contact the SVZ at all. Conclusion: Glioblastoma samples in the SVZ region are enriched for increased (epithelial-)mesenchymal transition and angiogenesis\/hypoxia signaling, possibly mediated by the SVZ microenvironment.<\/jats:p>","DOI":"10.3390\/cancers13153764","type":"journal-article","created":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T12:18:31Z","timestamp":1627388311000},"page":"3764","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Glioblastomas within the Subventricular Zone Are Region-Specific Enriched for Mesenchymal Transition Markers: An Intratumoral Gene Expression Analysis"],"prefix":"10.3390","volume":"13","author":[{"given":"Diana J. Z.","family":"Dalemans","sequence":"first","affiliation":[{"name":"UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon","family":"Berendsen","sequence":"additional","affiliation":[{"name":"UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaspar","family":"Draaisma","sequence":"additional","affiliation":[{"name":"UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"},{"name":"Department of Neurology, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7845-6196","authenticated-orcid":false,"given":"Pierre A.","family":"Robe","sequence":"additional","affiliation":[{"name":"UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"},{"name":"Department of Human Genetics, University Hospital Liege, 4000 Liege, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0857-081X","authenticated-orcid":false,"given":"Tom J.","family":"Snijders","sequence":"additional","affiliation":[{"name":"UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S1470-2045(09)70025-7","article-title":"Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial","volume":"10","author":"Stupp","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/nature02301","article-title":"Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration","volume":"427","author":"Sanai","year":"2004","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ccr.2008.12.006","article-title":"Malignant astrocytomas originate from neural stem\/progenitor cells in a somatic tumor suppressor mouse model","volume":"15","author":"Llaguno","year":"2009","journal-title":"Cancer Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/s41586-018-0389-3","article-title":"Human glioblastoma arises from subventricular zone cells with low-level driver mutations","volume":"560","author":"Lee","year":"2018","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Berendsen, S., van Bodegraven, E., Seute, T., Spliet, W.G.M., Geurts, M., Hendrikse, J., Schoysman, L., Huiszoon, W.B., Varkila, M., and Rouss, S. 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