title: Clinical and prognostic role of annexin A2 in adamantinomatous craniopharyngioma.
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.
authors.affiliation: West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Yuelong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, People's Republic of China. aipingtong@scu.edu.cn.
authors.forename: Aiping
authors.initials: A
authors.lastname: Tong
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, People's Republic of China.
authors.forename: Xirui
authors.initials: X
authors.lastname: Peng
authors.affiliation: West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Chen
authors.affiliation: West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xu
authors.affiliation: West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: You
authors.affiliation: West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, People's Republic of China. liangxue_zhou@126.com.
authors.forename: Liangxue
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003397:Craniopharyngioma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011379:Prognosis; D011799:Quinazolines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects; D055815:Young Adult
chemical_list: D017306:Annexin A2; D000970:Antineoplastic Agents; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D051058:Oncogene Protein v-akt; D000077156:Gefitinib
keywords: Adamantinomatous craniopharyngioma; Annexin A2; Gefitinib resistance; Proliferation; Recurrence