Treatment-Altered VEGF-Associated Network in GBM BVZ-Responsive Subtypes: Bioinformatics Case Studies

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Objective: As an anti-angiogenetic treatment, bevacizumab (BVZ) therapy for GBM patients targets vascular endothelial growth factor A (VEGF), which can significantly reduce tumor sizes in the early stage based on imaging studies.However, the related mechanism of the VEGF-associated network has not yet been elucidated.Recently, subtypes of GBM BVZ response were classified and detected, so the treatment effects and related mechanisms could be reassessed individually for these different subtypes.In this study, we want to further explore possible mechanisms, effects, and side effects of BVZ treatment in GBM patients based on bioinformatics analysis.Methods: We performed multiple statistical and bioinformatics studies on several mRNA expression profiles, from hundreds of GBM patients, including an mRNA profile from 20 GBM patients before and after BVZ treatment, based on the classification of GBM patients into BVZ-responsive and BVZ-nonresponsive subtypes.Furthermore, the expression levels of various genes in the VEGF-associated and unassociated networks before and after BVZ treatment were also compared in GBM BVZ subtypes using these datasets.Results: After BVZ treatment, mRNA expression patterns and functional pathways were very different between GBM BVZ-responsive and nonresponsive subtypes.Most importantly, Angpt1, SH2D2A, and LEF1 expression levels were significantly suppressed in the tissues of GBM BVZresponsive patients but not in the tissues of GMB BVZ-nonresponsive patients.According to bioinformatics analysis, there is a network connection between these genes and VEGF;therefore, the inhibition of these genes by BVZ treatment may occur through this network of V EGF.Notably, these results suggested that some aging-related side effects,possibly involving inEPHA1 and ESM1 and related networks, may result from the treatment of BVZ-nonresponsive GBM patients.Conclusions: Ang1, SH1D2A, and LEF1were associated with BVZ treatment in GBM BVZ-responsive patients, and the effects of these genes may act through the VEGF network as VEGF-associated or unassociated pathways.The study also revealed that there may be aging-related side effects caused by the treatment for GBM BVZ-nonresponsive patients, suggesting the need for predetection of GBM BVZ-responsive subtypes.However, further research in the field is needed to better understand the roles of these genes following BVZ treatment.

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