The abnormal expressions of enhancer-associated genes have been reported to be correlated with poor prognosis of tumors, including glioblastoma (GBM). The objective of the current study is to predict prognosis by identifying enhancer-associated genes (EAGs). The profiles of genome-wide expressions of low-grade glioma (LGG) and GBM tissues in The Cancer Genome Atlas (TCGA) dataset were obtained to explore the expression patterns of EAGs in diffuse glioma. The capacity of prognosis prediction was validated by Rembrandt and GSE16011. Moreover, qPCR was utilized to confirm the effect of JQ1 and THZ1 on the EAGs. We detected 35 differentially expressed EAGs, which were predictive of overall survival. These candidate EAGs were then subjected to the multivariate cox regression analysis and were further scoped down to four signature genes, including TRAM2, SMAGP, KDELC2, and C7ORF25. A total of 662 patients were then stratified according to the expression levels of these four signature genes. The high-risk group accounted for poorer prognosis based on the Rembrandt and GSE16011 databases. The results of qPCR also demonstrated that the expression of the four EAGs could be abolished by JQ1 (bromodomain inhibitor) and THZ1 (CDK7 inhibitor) treatment. Our study not only highlights the potential role of EAGs, which can be used to improve clinical prognosis prediction in patients with diffuse glioma, but also sheds light on the specific biomarkers and therapeutic targets for diffuse glioma patients.

据报道，增强子相关基因的异常表达与包括胶质母细胞瘤 (GBM) 在内的肿瘤的不良预后相关。当前研究的目的是通过识别增强子相关基因 (EAG) 来预测预后。获得了癌症基因组图谱 (TCGA) 数据集中低级别胶质瘤 (LGG) 和 GBM 组织的全基因组表达谱，以探索弥漫性胶质瘤中 EAG 的表达模式。Rembrandt 和 GSE16011 验证了预后预测的能力。此外，qPCR 用于确认 JQ1 和 THZ1 对 EAG 的影响。我们检测到 35 个差异表达的 EAG，它们可以预测总生存期。然后对这些候选 EAG 进行多变量 cox 回归分析，并进一步缩小到四个特征基因，包括 TRAM2、SMAGP、KDELC2 和 C7ORF25。然后根据这四个特征基因的表达水平对总共 662 名患者进行分层。根据伦勃朗和 GSE16011 数据库，高风险组的预后较差。qPCR 的结果还表明 JQ1（溴结构域抑制剂）和 THZ1（CDK7 抑制剂）处理可以消除四种 EAG 的表达。我们的研究不仅突出了 EAG 的潜在作用，可用于改善弥漫性神经胶质瘤患者的临床预后预测，而且还阐明了弥漫性神经胶质瘤患者的特定生物标志物和治疗靶点。根据伦勃朗和 GSE16011 数据库，高风险组的预后较差。qPCR 的结果还表明 JQ1（溴结构域抑制剂）和 THZ1（CDK7 抑制剂）处理可以消除四种 EAG 的表达。我们的研究不仅突出了 EAG 的潜在作用，可用于改善弥漫性神经胶质瘤患者的临床预后预测，而且还阐明了弥漫性神经胶质瘤患者的特定生物标志物和治疗靶点。根据伦勃朗和 GSE16011 数据库，高风险组的预后较差。qPCR 的结果还表明 JQ1（溴结构域抑制剂）和 THZ1（CDK7 抑制剂）处理可以消除四种 EAG 的表达。我们的研究不仅突出了 EAG 的潜在作用，可用于改善弥漫性神经胶质瘤患者的临床预后预测，而且还阐明了弥漫性神经胶质瘤患者的特定生物标志物和治疗靶点。