J Pathol Transl Med.  2022 Jul;56(4):205-211. 10.4132/jptm.2022.04.22.

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

• da Costa BHB
• Becker AP
• Neder L
• Gonçalves PG
• de Oliveira C
• Polverini AD
• Clara CA
• Teixeira GR
• Reis RM
• Bidinotto LT

• KMID: 2531612
• DOI: http://doi.org/10.4132/jptm.2022.04.22

Abstract

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.

Keyword

EGFL7; Glioblastoma IDH-wildtype; PI3K-Akt pathway; Notch pathway; Rap1 pathway

Figure

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  Fig. 1 Kyoto Encyclopedia of Genes and Genomes pathway and gene ontology (GO, biological processes) enrichment analysis of the genes highly correlated to EGFL7 expression. The sizes and color of the bubbles indicate the number of genes per term and significance level. EGFL7, epidermal growth factor-like domain multiple 7.

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  Fig. 2 Overall survival curves of glioblastoma patients. (A) In silico data of The Cancer Genome Atlas (TCGA) RNA sequencing. (B) Data of protein expression from 74 patients detected through immunohistochemistry. p-values were calculated using log-rank analysis. EGFL7, epidermal growth factor-like domain multiple 7.

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  Fig. 3 Microphotographs of resected specimens of glioblastomas immunostained for EGFL7. (A) Absence of immunoreactivity, although vascular endothelial cells serve as a positive internal control for EGFL7. (B) Diffuse and strong EGFL7 immunoreactivity. EGFL7, epidermal growth factor-like domain multiple 7.

Reference

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