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Many GB patients do not respond to treatment, and inevitably die within a median of 15\u201318 months post-diagnosis, highlighting the need for reliable biomarkers to aid clinical management and treatment evaluation. The GB microenvironment holds tremendous potential as a source of biomarkers; several proteins such as MMP-2, MMP-9, YKL40, and VEGFA have been identified as being differentially expressed in GB patient samples. Still to date, none of these proteins have been translated into relevant clinical biomarkers. This study evaluated the expression of MMP-2, MMP-9, YKL40, and VEGFA in a series of GBs and their impact on patient outcome. High levels of VEGFA expression were significantly associated with improved progression-free survival after bevacizumab treatment, thus having potential as a tissue biomarker for predicting patients\u2019 response to bevacizumab. Noteworthily, VEGFA expression was not associated with patient outcome after temozolomide treatment. To a lesser extent, YKL40 also provided significant information regarding the extent of bevacizumab treatment. This study highlights the importance of studying secretome-associated proteins as GB biomarkers and identifies VEGFA as a promising marker for predicting response to bevacizumab.<\/jats:p>","DOI":"10.3390\/cancers15082196","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T03:19:54Z","timestamp":1681096794000},"page":"2196","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["High VEGFA Expression Is Associated with Improved Progression-Free Survival after Bevacizumab Treatment in Recurrent Glioblastoma"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1743-6022","authenticated-orcid":false,"given":"B\u00e1rbara","family":"Alves","sequence":"first","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, 4200 Porto, Portugal"},{"name":"Cancer Signalling & Metabolism Group, IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, 4200 Porto, Portugal"},{"name":"School of Allied Health Sciences, Polytechnic Institute of Porto, 4200 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9469-5680","authenticated-orcid":false,"given":"Joana","family":"Peixoto","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, 4200 Porto, Portugal"},{"name":"Cancer Signalling & Metabolism Group, IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, 4200 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7752-998X","authenticated-orcid":false,"given":"Sofia","family":"Macedo","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, 4200 Porto, Portugal"},{"name":"Cancer Signalling & Metabolism Group, IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, 4200 Porto, Portugal"}]},{"given":"Jorge","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"Department of Pathology, Centro Hospitalar Universit\u00e1rio S. Jo\u00e3o, 4200 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3972-7544","authenticated-orcid":false,"given":"Bruno","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Centro Hospitalar Universit\u00e1rio S. Jo\u00e3o, 4200 Porto, Portugal"},{"name":"FMUP\u2014Faculty of Medicine of the University of Porto, 4200 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9607-6998","authenticated-orcid":false,"given":"Paula","family":"Soares","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, 4200 Porto, Portugal"},{"name":"Cancer Signalling & Metabolism Group, IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, 4200 Porto, Portugal"},{"name":"Department of Pathology, FMUP\u2014Faculty of Medicine of the University of Porto, 4200 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7780-0901","authenticated-orcid":false,"given":"Jorge","family":"Lima","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, 4200 Porto, Portugal"},{"name":"Cancer Signalling & Metabolism Group, IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, 4200 Porto, Portugal"},{"name":"Department of Pathology, FMUP\u2014Faculty of Medicine of the University of Porto, 4200 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5838-9659","authenticated-orcid":false,"given":"Raquel T.","family":"Lima","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, 4200 Porto, Portugal"},{"name":"Cancer Signalling & Metabolism Group, IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, 4200 Porto, Portugal"},{"name":"Department of Pathology, FMUP\u2014Faculty of Medicine of the University of Porto, 4200 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.2147\/CMAR.S186142","article-title":"The Unique Invasiveness of Glioblastoma and Possible Drug Targets on Extracellular Matrix","volume":"11","author":"Hatoum","year":"2019","journal-title":"Cancer Manag. 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