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

ABSTRACT: 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 EGFR-positive 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. Consensus-clustering 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 activator in 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.

SUBMITTER: Wang FY 

PROVIDER: S-EPMC7571400 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature