Journal of Pathology and Translational Medicine

Original Article

EGFL7 expression profile in IDH-wildtype glioblastomas is associated with poor patient outcome: Bruno Henrique Bressan da Costa, Aline Paixão Becker, Luciano Neder, Paola Gyuliane Gonçalves, Cristiane de Oliveira, Allan Dias Polverini, Carlos Afonso Clara, Gustavo Ramos Teixeira, Rui Manuel Reis, Lucas Tadeu Bidinotto; J Pathol Transl Med. 2022;56(4):205-211. Published online June 15, 2022; DOI: https://doi.org/10.4132/jptm.2022.04.22

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Background
Despite the advances in glioblastoma (GBM) treatment, the average life span of patients is 14 months. Therefore, it is urgent 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 astrocytoma 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 sequencing 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 survival. The expression of EGFL7 was analyzed through immunohistochemistry in 74 GBM IDH-wildtype patients’ samples, and was associated with clinicopathological data and overall survival.
Results
In silico analysis found 78 genes strongly correlated to EGFL7 expression. 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 expression 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.

Citations

Citations to this article as recorded by

Role of EGFL7 in human cancers: A review
Cristiane de Oliveira, Paola Gyuliane Gonçalves, Lucas Tadeu Bidinotto
Journal of Cellular Physiology.2023; 238(8): 1756. CrossRef
Low EGFL7 expression is associated with high lymph node spread and invasion of lymphatic vessels in colorectal cancer
Cristiane de Oliveira, Sandra Fátima Fernandes Martins, Paola Gyuliane Gonçalves, Gabriel Augusto Limone, Adhemar Longatto-Filho, Rui Manuel Reis, Lucas Tadeu Bidinotto
Scientific Reports.2023;[Epub] CrossRef

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