10125-ANGI-1 Comparative analyses of Annexin A2 expression and prognosis during bevacizumab therapy in glioblastoma between effectiveness and refractoriness

Abstract Background Glioblastoma (GBM) has a dismal prognosis, with limited survival benefit from bevacizumab (Bev). Annexin A2 (ANXA2), a molecule involved in angiogenesis and invasion, may play a key role in resistance mechanisms. The aim of the present study was to compare ANXA2 expression and clinical outcome in newly diagnosed GBM by Bev therapy. Methods We analyzed 65 samples from 33 patients with GBM, consisting of initial (Naïve Bev; n = 15), neoadjuvant Bev (NeoBev; n = 18), and recurrent tumors (Refractory Bev) including paired samples. Progression-free survival (PFS), and overall survival (OS) were assessed by stratification of ANXA2 expression quantitated by qPCR with comparison of MRI with or without contrast medium. Results In the Naïve Bev group, ANXA2 expression was not associated with clinical prognosis. Whereas in the NeoBev group, low level of ANXA2 expression revealed favorable PFS (p = 0.1062) and OS (p = 0.0025), suggesting that high ANXA2 levels at the naïve stage resulted in a rapid decrease of expression after NeoBev and providing simultaneous suppression of angiogenesis and invasion, leading to favorable prognosis. As for impact of cumulative Bev administrations stratified by treatment cycle count (<15 vs. ≥15 cycles), ANXA2 expression was significantly lower in patients with ≥ 15 cycles compared with those with <15 cycles (p = 0.0367). In particular, patients with lower expression in NeoBev group revealed prolongation of OS. T1Gd good responders showed a trend toward longer PFS (p = 0.1037), while T2/FLAIR poor responders also showed a similar trend (p = 0.0688). In addition, there were no significance between ANXA2 expression level and recurrent pattern on MRI in both of Naïve and NeoBev. Conclusion ANXA2 may reflect treatment-related imaging changes and be involved in both angiogenesis and invasion. These findings suggest that ANXA2 could provide not only as a prognostic factor but also as a predictive biomarker for response to neoadjuvant Bev therapy.