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

Cancers (Basel). 2023 Apr 7;15(8):2196. doi: 10.3390/cancers15082196.

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.

Keywords: MMP-2; MMP-9; VEGFA; YKL40; biomarkers; glioblastoma; immunohistochemistry; secretome.