Proteomics identifies EGF-like domain multiple 7 as a potential therapeutic target for epidermal growth factor receptor-positive glioma  

作　　者：Fei-yi-fan Wang Si-yi Wang-gou Hang Cao Nian Jiang Qi Yang Qi Huang Chun-hai Huang Xue-jun Li 

机构地区：[1]Department of Neurosurgery,Xiangya Hospital,Central South University,Changsha,Hunan 410008,P.R.China [2]Department of Neurosurgery,the First Affiliated Hospital of Jishou University,Jishou,Hunan 416000,P.R.China [3]Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research,Xiangya Hospital,Central South University,Changsha,Hunan 410008,P.R.China

出　　处：《Cancer Communications》2020年第10期518-530,共13页癌症通讯（英文）

基　　金：This work was supported by grants from the National Natural Science Foundation of China(81770781 to XJL);Hunan Provincial Innovation Foundation for Postgraduate(CX2018B114 to FYFW);the Fundamental Research Funds for the Central Universities of Central South University(2018zzts043 to FYFW);China Scholarship Council(201806370130 to FYFW).

摘　　要：Background:Glioma,the most frequent primary tumor of the central nervous system,has poor prognosis.The epidermal growth factor receptor(EGFR)pathway and angiogenesis play important roles in glioma growth,invasion,and recurrence.The present study aimed to use proteomic methods to probe into the role of the EGF-EGFR-angiogenesis axis in the tumorigenesis of glioma and access the therapeutic efficacy of selumetinib on glioma.Methods:Proteomic profiling was used to characterize 200 paired EGFRpositive and EGFR-negative glioma tissues of all pathological types.The quantitative mass spectrometry data were used for systematic analysis of the proteomic profiles of 10 EGFR-positive and 10 EGFR-negative glioma cases.Consensusclustering analysis was used to screen target proteins.Immunofluorescence analysis,cell growth assay,and intracranial xenograft experiments were used to verify and test the therapeutic effect of selumetinib on glioma.Results:Advanced proteomic screening demonstrated that the expression of EGF-like domain multiple 7(EGFL7)was higher in EGFR-positive tumor tissues than in EGFR-negative tumor tissues.In addition,EGFL7 could act as an activatorin vitro and in vivo to promote glioma cell proliferation.EGFL7 was associated strongly with EGFR and prognosis.EGFL7 knockdown effectively suppressed glioma cell proliferation.Selumetinib treatment showed tumor reduction effect in EGFR-positive glioblastoma xenograft mouse model.Conclusions:EGFL7 is a potential diagnostic biomarker and therapeutic target of glioma.Selumetinib could target the EGFR pathway and possibly improve the prognosis of EGFR-positive glioma.

关 键 词：GLIOMA PROTEOMICS Epidermal growth factor receptor EGF-like domain multiple 7 Targeted therapy SELUMETINIB 

分 类 号：R73[医药卫生—肿瘤]