High VEGFA Expression Is Associated with Improved Progression-Free Survival after Bevacizumab Treatment in Recurrent Glioblastoma

SIMPLE SUMMARY: Glioblastoma (GB) is a deadly tumor that demands for relevant biomarkers, particularly regarding patients’ response to treatment. MMP-2, MMP-9, VEGFA, and YKL40 are important molecules, given their implication in the infiltrative and angiogenic phenotype of GBs. The purpose of this study was to assess the relationship between the expression of MMP-2, MMP-9, VEGFA, and YKL40 in GB tissues and the patients’ response to temozolomide (first-line treatment) or bevacizumab (second-line treatment). Our results showed that increased VEGFA is significantly associated with an improved response to bevacizumab, while having no correlation with the response to temozolomide. Additionally, YKL40 expression may also be important regarding information about the extent of antiangiogenic treatment in GB patients. ABSTRACT: Glioblastoma (GB) is one of the deadliest human cancers. Many GB patients do not respond to treatment, and inevitably die within a median of 15–18 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’ 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.