da Costa Bruno Henrique Bressan, Becker Aline Paixão, Neder Luciano, Gonçalves Paola Gyuliane, de Oliveira Cristiane, Polverini Allan Dias, Clara Carlos Afonso, Teixeira Gustavo Ramos, Reis Rui Manuel, Bidinotto Lucas Tadeu
Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
Barretos School of Health Sciences, Dr. Paulo Prata - FACISB, Barretos, São Paulo, Brazil.
J Pathol Transl Med. 2022 Jul;56(4):205-211. doi: 10.4132/jptm.2022.04.22. Epub 2022 Jun 15.
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.
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.
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).
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.
尽管胶质母细胞瘤（GBM）治疗取得了进展，但患者的平均寿命仍为14个月。因此，迫切需要确定预后、治疗反应或新型治疗策略发展的生物标志物。我们之前描述了高表皮生长因子样结构域多重7（EGFL7）表达与毛细胞型星形细胞瘤患者不良预后的关联。本研究旨在使用免疫组织化学和计算机分析方法分析EGFL7在GBM异柠檬酸脱氢酶（IDH）野生型中的预后潜力。
对癌症基因组图谱RNA测序数据进行Spearman相关性分析。将与EGFL7表达强烈相关的基因提交至基因本体富集分析和京都基因与基因组百科全书（KEGG）分析。此外，EGFL7表达与患者总生存期相关。通过免疫组织化学分析74例GBM IDH野生型患者样本中EGFL7的表达，并将其与临床病理数据和总生存期相关联。
计算机分析发现78个基因与EGFL7表达强烈相关。这些基因富集于40个生物学过程和8条KEGG通路，包括血管生成/血管发生、细胞黏附以及磷脂酰肌醇3-激酶-Akt、Notch和Rap1信号通路。免疫染色显示39例（52.7%）EGFL7高表达。高免疫标记与低卡诺夫斯基功能状态和不良总生存期显著相关。Cox分析显示，与低表达相比，EGFL7高表达的GBM IDH野生型死亡风险更高（风险比，1.645；95%置信区间，1.021至2.650；p = 0.041）。
本研究提供了与EGFL7相关的基因以及生物学过程和信号通路的相关见解，为阐明它们在胶质母细胞瘤生物学中的作用，应进一步开展研究。
