GENE-38. DISRUPTED ENDOTHELIAL CELL GENE EXPRESSION PROFILE PREDICTS GBM CLINICAL RESPONSE TO ANTI-ANGIOGENIC THERAPY

Abstract

Glioblastoma (GBM) is one of the most aggressive adult brain tumors, with the histopathologic hallmark of increased abnormal vasculature. While anti-angiogenesis therapy had shown value in pre-clinical and early clinical studies, in particular targeting vascular endothelial growth factor (VEGF), the durability of response to anti-angiogenic therapy varies and hence efficacy remains a limitation. There is data to suggest that certain subtypes of GBM however have a more effective response to anti-angiogenic therapy. Therefore, there is a need to identify prognostic markers that can determine the subpopulation of GBM patients that response to AA therapy. We established five genetic expression profiles (group A~E) by stimulating endothelial cells (ECs) with different combinations of ionizing radiation (IR) and mesenchymal stem cells (MSCs) before performing angiogenesis array analysis. Bioinformatics analysis of Group A~E identified the combination of HGF and CXCL10 alterations as the differentiators that separated the AVAglio patients into 3 groups (group 1~3). We found that GBM patients with high HGF and low CXCL10 levels had the worst clinical response to AA therapy. Further qPCR analysis of gene expression levels among different cell types revealed that GBM cells have the highest expression of HGF and the lowest expression of CXCL10 relative to ECs. Similar trend were detected in MSCs relative to ECs but to a lesser degree. Thus we propose that such genetic parameter in GBM could potentially be a prognostic marker for AA therapy.