列线图
Erg公司
基因
一致性
增强子
接收机工作特性
医学
胶质瘤
肿瘤科
基因表达
计算生物学
生物
生物信息学
内科学
癌症研究
遗传学
眼科
视网膜
作者
Wei Tian,Guangcan Yan,Kegong Chen,Xinhao Han,Wei Zhang,Lin Sun,Qi Zhang,Yafeng Zhang,Yan Li,Meina Liu,Qiuju Zhang
标识
DOI:10.3389/fonc.2022.714338
摘要
Enhancer RNAs (eRNAs) are present specifically in tumors, where they affect the expression of eRNA-regulated genes (ERGs). Owing to this characteristic, ERGs were hypothesized to improve prognosis of overall survival in heterogeneous low-grade and intermediate-grade gliomas. This study aimed to construct and validate an ERG prognostic tool to facilitate clinical management, and offer more effective diagnostic and therapeutic biomarkers for glioma. Survival-related eRNAs were identified, and their ERGs were selected based on eRNA and target gene information. The ERG prognostic model was constructed and validated using internal and external validation cohorts. Finally, biological differences related to the ERG signature were analysed to explore the potential mechanisms influencing survival outcomes. Thirteen ERGs were identified and used to build an ERG risk signature, which included five super-enhancer RNA (seRNA)-regulated genes and five LGG-specific eRNA-regulated genes. The prognostic nomogram established based on combining the ERG score, age, and sex was evaluated by calibration curves, clinical utility, Harrell's concordance index (0.86; 95% CI: 0.83-0.90), and time-dependent receiver operator characteristic curves. We also explored potential immune-related mechanisms that might cause variation in survival. The established prognostic model displayed high validity and robustness. Several immune-related genes regulated by seRNAs or specific eRNAs were identified, indicating that these transcripts or their genes were potential targets for improving immunotherapeutic/therapeutic outcomes. The functions of an important specific eRNA-regulated gene (USP28) were validated in robust vitro experiments. In addition, the ERG risk signature was significantly associated with the immune microenvironment and other immune-related features.
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