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17.09.2016 | Laboratory Investigation | Ausgabe 1/2017

Journal of Neuro-Oncology 1/2017

Clinical and prognostic role of annexin A2 in adamantinomatous craniopharyngioma

Zeitschrift:
Journal of Neuro-Oncology > Ausgabe 1/2017
Autoren:
Yuelong Wang, Jiaojiao Deng, Gang Guo, Aiping Tong, Xirui Peng, Haifeng Chen, Jianguo Xu, Yi Liu, Chao You, Liangxue Zhou
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s11060-016-2273-z) contains supplementary material, which is available to authorized users.
Jiaojiao Deng and Yuelong Wang have contributed equally to this paper, and Jiaojiao Deng is the co-first author of this paper.

Abstract

Annexin A2 (AnxA2) is a highly conserved Ca2+-regulated membrane binding protein, which affects cell mobility and tumor progression. Adamantinomatous craniopharyngioma (AdaCP) are a kind of epithelial tumors of the sellar region with high tendency to recur. Robust biomarkers are required to predict tumor behavior and to establish follow-up individualized treatment approaches. In this study, we firstly compared four surgical AdaCP samples with normal brain by two-dimensional gel electrophoresis (2DE) proteomic analysis. Potential prognostic biomarkers were further validated in a large cohort of 65 AdaCPs by immunohistochemistry. The effects of AnxA2 on AdaCP cells proliferation and migration were analyzed in vitro with isolated primary AdaCP cells as well as SV40T-immortalized cells. Finally, the gefitinib sensitivity of AdaCPs with differentially expressed AnxA2 and the potential molecular mechanisms were examined by flow cytometric analysis, Real-time PCR and immunoblot assays. Proteomic analysis indicated that AnxA2 was the protein spot with the most elevated expression in AdaCP samples. Immunohistochemistry assays indicated the expression level of AnxA2 was significantly higher in recurrent AdaCPs compared with primary ones. Moreover, AnxA2+ AdaCP cells exhibited enhanced proliferation and migration ability compared with AnxA2 AdaCP cells in vitro. Further, we show that AnxA2+ AdaCP cells exhibited elevated expression of EGFR and downstream p-AKT (S308) and p-AKT (S473), and were more sensitive to tyrosine kinase inhibitor gefitinib. Our data suggest that AnxA2 may serve as a promising biomarker for AdaCP progression, recurrence and drug susceptibility. Our data support potential clinical implications for the follow-up treatment of AdaCP patients with high AnxA2 expression.

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Zusatzmaterial
Supplementary material 1 (DOC 49 KB)
11060_2016_2273_MOESM1_ESM.doc
Literatur
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