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EGFL7 expression profile in IDH-wildtype glioblastomas is associated with poor patient outcome

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da Costa, Bruno Henrique Bressan ; Becker, Aline Paixao ; Neder, Luciano ; Goncalves, Paola Gyuliane ; de Oliveira, Cristiane ; Polverini, Allan Dias ; Clara, Carlos Afonso ; Teixeira, Gustavo Ramos ; Reis, Rui Manuel ; Bidinotto, Lucas Tadeu
Total Authors: 10
Document type: Journal article

Background: Despite the advances in glioblastoma (GBM) treatment, the average life span of patients is 14 months. Therefore, it is ur -gent to identity biomarkers of prognosis, treatment response, or development of novel treatment strategies. We previously described the association of high epidermal growth factor-like domain multiple 7 (EGFL7) expression and unfavorable outcome of pilocytic astro-cytoma patients. The present study aims to analyze the prognostic potential of EGFL7 in GBM isocitrate dehydrogenase (IDH)-wildtype, using immunohistochemistry and in silico approaches. Methods: Spearman's correlation analysis of The Cancer Genome Atlas RNA se-quencing data was performed. The genes strongly correlated to EGFL7 expression were submitted to enrichment gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Additionally, EGFL7 expression was associated with patient overall sur-vival. The expression of EGFL7 was analyzed through immunohistochemistry in 74 GBM IDH-wildtype patients' samples, and was as-sociated with clinicopathological data and overall survival. Results: In silico analysis found 78 genes strongly correlated to EGFL7 ex -pression. These genes were enriched in 40 biological processes and eight KEGG pathways, including angiogenesis/vasculogenesis, cell adhesion, and phosphoinositide 3-kinase-Akt, Notch, and Rap1 signaling pathways. The immunostaining showed high EGFL7 expres-sion in 39 cases (52.7%). High immunolabelling was significantly associated with low Karnofsky Performance Status and poor overall survival. Cox analysis showed that GBMs IDH-wildtype with high EGFL7 expression presented a higher risk of death compared to low expression (hazard ratio, 1.645; 95% confidence interval, 1.021 to 2.650; p = .041). Conclusions: This study gives insights regarding the genes that are correlated with EGFL7, as well as biological processes and signaling pathways, which should be further investigated in order to elucidate their role in glioblastoma biology. (AU)

FAPESP's process: 18/20737-1 - Evaluation of the expression of EGFL7 in glioblastoma and its correlation with clinicopathological data
Grantee:Bruno Henrique Bressan da Costa
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 17/09749-5 - Evaluation of the expression and potential prognosis of the genes present in the chr9p22.1-p21.3 locus in gliomas
Grantee:Paola Gyuliane Gonçalves
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 16/21727-4 - Analysis of the prognostic potential of the genes present in the locus 9p22.1-p21.3 in gliomas
Grantee:Lucas Tadeu Bidinotto
Support Opportunities: Regular Research Grants