Department of Neurosurgery, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, Hefei, China.
Department of Neurosurgery, Chuzhou Clinical College of Anhui Medical University, The First People's Hospital Chuzhou, Chuzhou, China.
J Cell Mol Med. 2021 Jan;25(2):925-936. doi: 10.1111/jcmm.16149. Epub 2020 Dec 4.
The enhancer of zeste homologue 2 (EZH2) is a histone H3 lysine 27 methyltransferase that promotes tumorigenesis in a variety of human malignancies by altering the expression of tumour suppressor genes. To evaluate the prognostic value of EZH2 in glioma, we analysed gene expression data and corresponding clinicopathological information from the Chinese Glioma Genome Atlas, the Cancer Genome Atlas and GTEx. Increased expression of EZH2 was significantly associated with clinicopathologic characteristics and overall survival as evaluated by univariate and multivariate Cox regression. Gene Set Enrichment Analysis revealed an association of EZH2 expression with the cell cycle, DNA replication, mismatch repair, p53 signalling and pyrimidine metabolism. We constructed a nomogram for prognosis prediction with EZH2, clinicopathologic variables and significantly correlated genes. EZH2 was demonstrated to be significantly associated with several immune checkpoints and tumour-infiltrating lymphocytes. Furthermore, the ESTIMATE and Timer Database scores indicated correlation of EZH2 expression with a more immunosuppressive microenvironment for glioblastoma than for low grade glioma. Overall, our study demonstrates that expression of EZH2 is a potential prognostic molecular marker of poor survival in glioma and identifies signalling pathways and immune checkpoints regulated by EHZ2, suggesting a direction for future application of immune therapy in glioma.
增强子结合锌指蛋白 2（EZH2）是一种组蛋白 H3 赖氨酸 27 甲基转移酶，通过改变肿瘤抑制基因的表达，在多种人类恶性肿瘤中促进肿瘤发生。为了评估 EZH2 在神经胶质瘤中的预后价值，我们分析了来自中国神经胶质瘤基因组图谱、癌症基因组图谱和 GTEx 的基因表达数据和相应的临床病理信息。单因素和多因素 Cox 回归分析表明，EZH2 的表达增加与临床病理特征和总生存期显著相关。基因集富集分析显示，EZH2 表达与细胞周期、DNA 复制、错配修复、p53 信号和嘧啶代谢有关。我们构建了一个基于 EZH2、临床病理变量和显著相关基因的预后预测列线图。EZH2 与几个免疫检查点和肿瘤浸润淋巴细胞显著相关。此外，ESTIMATE 和 Timer 数据库评分表明，与低级别神经胶质瘤相比，EZH2 表达与胶质母细胞瘤更具免疫抑制的微环境相关。总之，我们的研究表明，EZH2 的表达是神经胶质瘤不良生存的潜在预后分子标志物，并确定了 EHZ2 调节的信号通路和免疫检查点，为神经胶质瘤的免疫治疗提供了新的方向。
