Annexin A2 associated with bevacizumab resistance and infiltrative escape in glioblastoma

Résumé fourni par la source

BACKGROUND: The clinical benefit of bevacizumab (Bev) in glioblastoma (GBM) is typically transient, as tumors develop adaptive resistance characterized by an infiltrative shift from angiogenesis dependent growth. This study investigated Annexin A2 (ANXA2), a regulator of both angiogenesis and invasion, as a potential biomarker of Bev resistance. METHODS: We analyzed 66 tissue-specimens from 33 GBM patients using quantitative real-time PCR and immunohistochemistry/immunofluorescence. The cohort included 15 Bev-naïve cases and 18 neoadjuvant Bev (neoBev) cases. 33 refractory specimens-including unique paired samples from the same patients at different treatment phases (initial resection vs. refractory stage) were evaluated to correlate ANXA2 expression levels with progression-free survival (PFS), overall survival (OS), and MRI recurrence patterns. RESULTS: Multivariate analysis identified high ANXA2 expression as a significant independent poor prognostic factor for both PFS and OS. In the neoBev group, patients with low ANXA2 mRNA expression levels demonstrated significantly superior survival outcome compared to those with high expression. While ANXA2 mRNA levels tended to increase at the refractory stage, a significant negative correlation was observed between the number of Bev cycles and ANXA2 expression levels. Histopathological analyses revealed intense ANXA2 expression in the tumor vasculature and stroma at the GBM leading edge, co-localization with the hypoxia marker hypoxia-inducible factor-1α. CONCLUSIONS: ANXA2 may serve as a predictive biomarker of the adaptive transition from an angiogenic to infiltrative phenotype with Bev therapy. These findings suggest that ANXA2 serves as a predictive biomarker for Bev clinical benefit and may represent a candidate therapeutic target requiring further validation in GBM.