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.
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.
摘要：
背景：尽管胶质母细胞瘤（GBM）的治疗取得了进展，患者的平均寿命为14个月。因此,迫切需要确定预后的生物标志物，治疗反应,或开发新的治疗策略。我们先前描述了高表皮生长因子样结构域多重7（EGFL7）表达与毛细胞性星形细胞瘤患者的不利结果的关联。本研究旨在分析EGFL7在GBM异柠檬酸脱氢酶（IDH）野生型中的预后潜力，使用免疫组织化学和计算机模拟方法。
方法：对癌症基因组图谱RNA测序数据进行Spearman的相关性分析。将与EGFL7表达强烈相关的基因提交至富集基因本体论和京都基因和基因组百科全书(KEGG)分析。此外,EGFL7表达与患者总生存期相关。EGFL7的表达通过免疫组织化学在74GBMIDH-野生型患者\'样本中进行分析，并与临床病理资料和总生存率相关。
结果：计算机模拟分析发现78个基因与EGFL7表达密切相关。这些基因富集在40个生物过程和8个KEGG通路中，包括血管生成/血管生成，细胞粘附，和磷酸肌醇3-激酶-Akt，缺口,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Karnofsky性能状态和低总生存率显着相关。Cox分析表明，与低表达相比，具有高EGFL7表达的GBMsIDH野生型呈现更高的死亡风险（风险比，1.645；95%置信区间，1.021至2.650；p=.041）。
结论：这项研究提供了有关与EGFL7相关的基因以及生物过程和信号通路的见解。应进一步研究以阐明其在胶质母细胞瘤生物学中的作用。
方法：对癌症基因组图谱RNA测序数据进行Spearman的相关性分析。将与EGFL7表达强烈相关的基因提交至富集基因本体论和京都基因和基因组百科全书(KEGG)分析。此外,EGFL7表达与患者总生存期相关。EGFL7的表达通过免疫组织化学在74GBMIDH-野生型患者\'样本中进行分析，并与临床病理资料和总生存率相关。
结果：计算机模拟分析发现78个基因与EGFL7表达密切相关。这些基因富集在40个生物过程和8个KEGG通路中，包括血管生成/血管生成，细胞粘附，和磷酸肌醇3-激酶-Akt，缺口,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Karnofsky性能状态和低总生存率显着相关。Cox分析表明，与低表达相比，具有高EGFL7表达的GBMsIDH野生型呈现更高的死亡风险（风险比，1.645；95%置信区间，1.021至2.650；p=.041）。
结论：这项研究提供了有关与EGFL7相关的基因以及生物过程和信号通路的见解。应进一步研究以阐明其在胶质母细胞瘤生物学中的作用。
