目标：新兴的证据显示，超级增强子在许多癌症的转录重编程中发挥关键作用。本研究旨在探讨超级增强子相关基因如何影响低级别胶质瘤（LGG）患者的预后和肿瘤免疫微环境（TIME）。方法：本研究通过综合分析超级增强子（SE）相关基因，确定了LGG队列和正常脑组织队列之间的差异表达基因（DEGs）。然后进行非负矩阵分解，寻找基于DEGs的最佳分类，并调查不同亚型之间的预后和临床差异。随后，构建了一个预后相关签名（SERS），综合评估LGG患者的个体化预后、临床特征、癌症标志物、基因组改变和免疫微环境。结果：基于170个DEGs的表达谱，我们确定了三种SE亚型，这三种亚型在预后和临床病理特征方面呈现显著差异。然后，通过最小绝对收缩和选择算子Cox回归分析选择了9个最佳的SE相关基因构建了SERS。生存分析显示，SERS对The Cancer Genome Atlas、中国胶质瘤基因组图谱和Remdrandt队列中的LGG患者的预后具有强大且稳定的预测能力。我们还发现，SERS与LGG患者的临床病理特征、肿瘤免疫微环境、癌症标志物和基因组改变密切相关。此外，SERS对免疫检查点抑制剂治疗的预测能力也更优越。qRT-PCR结果和免疫组化结果也证实了四个关键基因在正常细胞和肿瘤中、正常组织和肿瘤组织中的表达差异。结论：SERS可适用于LGG患者的个体化预后预测和免疫治疗选择的临床应用。版权所有 © 2023年 Hu, Yang, Cai, Wang和Fu。

Objective: Emerging evidence revealed that super-enhancer plays a crucial role in the transcriptional reprogramming for many cancers. The purpose aimed to explored how the super-enhancer related genes affects the prognosis and tumor immune microenvironment (TIME) of patients with low-grade glioma (LGG). Methods: In this study, the differentially expressed genes (DEGs) between LGG cohorts and normal brain tissue cohort were identified by the comprehensive analysis of the super-enhancer (SE) related genes. Then non-negative matrix factorization was performed to seek the optimal classification based on the DEGs, while investigating prognostic and clinical differences between different subtypes. Subsequently, a prognostic related signature (SERS) was constructed for the comprehensive evaluation in term of individualized prognosis, clinical characteristics, cancer markers, genomic alterations, and immune microenvironment of patients with LGG. Results: Based on the expression profiles of 170 DEGs, we identified three SE subtypes, and the three subtypes showed significant differences in prognostic, clinicopathological features. Then, nine optimal SE-related genes were selected to construct the SERS through the least absolute shrinkage and selection operator Cox regression analysis. Survival analysis showed that SERS had strong and stable predictive ability for the prognosis of LGG patients in the The Cancer Genome Atlas, China Glioma Genome Atlas, and Remdrandt cohorts, respectively. We also found that SERS was highly correlated with clinicopathological features, tumor immune microenvironment, cancer hallmarks, and genomic alterations in LGG patients. In addition, the predictive power of SERS for immune checkpoint inhibitor treatment is also superior. The qRT-PCR results and immunohistochemical results also confirmed the difference in the expression of four key genes in normal cells and tumors, as well as in normal tissues and tumor tissues. Conclusion: The SERS could be suitable to utilize individualized prognosis prediction and immunotherapy options for LGG patients in clinical application.Copyright © 2023 Hu, Yang, Cai, Wang and Fu.