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EGFL7 EXPRESSION PROFILE IN GLIOBLASTOMA IS ASSOCIATED WITH POOR PATIENT OUTCOME
Introduction, Objectives, Methods, Results, and Conclusion.
Background: The average life span of patients with glioblastoma (GBM) is of 14 months despite the advances in GBM treatment. Thus, there is a need to identity biomarkers of prognostic and treatment response to be able to development new novel treatment strategies. EGFL7 is a pro-angiogenic factor that might play a role in tumor progression through mediation of metastasis, proliferation, and angiogenesis. A recent study showed that anti-EGFL7 (in combination with anti-VEGF/bevacizumab and TMZ) is able to inhibit angiogenesis and prolong survival in murine glioma xenograft models. Also, we previously described the association of high EGFL7 expression and unfavorable outcome of pilocytic astrocytoma patients. Thus, the present study aims to analyze the biological processes and possible prognostic role of EGFL7 in GBM, using immunohistochemistry and in silico approaches. Methods: The Cancer Genome Atlas (TCGA) RNA sequencing data was used to perform Spearman’s correlation analysis. The genes strongly correlated to EGFL7 expression were submitted to enrichment Gene Ontology and KEGG analysis. Additionally, EGFL7 expression was associated with patient overall survival. The expression of EGFL7 was analyzed in 78 GBM patients through immunohistochemistry (IHC), and was associated to clinicopathological data and overall survival. Results: The In silico analysis found 78 genes strongly correlated to the expression of EGFL7. These genes were enriched in 40 biological processes and 8 KEGG pathways, which included angiogenesis/vasculogenesis, cell adhesion process and PI3K-Akt, Notch and Rap1 signaling pathways. IHC showed high EGFL7 expression in 39 GBMs (50.0%). In addiction, the high immunostaining was significantly associated to low KPS and poor overall survival. Cox analysis showed that GBMs with high EGFL7 expression presented a 1.61-higher risk of death. Conclusions: This study gives insights regarding biological processes and signaling pathways related to EGFL7 expression as well the genes that are correlated with EGFL7, which should be further investigated in order to elucidate their role in glioblastoma biology and to develop new novel treatment strategies that will impact in the overall survival of GBM patients.
Keywords (separated by comma on a single line)
EGFL7, Glioblastoma, PI3K-Akt pathway, Notch pathway, Rap1 pathway
PAOLA GYULIANE GONÇALVES, BRUNO HENRIQUE BRESSAN DA COSTA, ALINE PAIXÃO BECKER, LUCIANO NEDER, CRISTIANE DE OLIVEIRA, CARLOS AFONSO CLARA, RUI MANUEL REIS, LUCAS TADEU BIDINOTTO