Identification of Four Enhancer-Associated Genes as Risk Signature for Diffuse Glioma Patients

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.