Zeng Jing, Sun Lu, Huang Jiaming, Yang Xia, Hu Wanming
Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China.
State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, China.
Front Neurosci. 2022 Nov 30;16:1076530. doi: 10.3389/fnins.2022.1076530. eCollection 2022.
Enhancer of zeste homolog 2 (EZH2), an important epigenetic regulator, that mainly regulates histone H3 lysine 27 trimethylation (H3K27me3) through histone methyltransferase, and participates in promoting the development of tumors. At present, the loss of H3K27me3 expression in meningioma is a poor prognostic factor, but the research of EZH2 in meningioma is rare. Therefore, we aim to explore the expression of EZH2 in the meningioma and its correlation with the prognosis and immune microenvironment and lay the foundation for the subsequently potential targeted therapy and immunotherapy for meningioma.
Tissue microarray immunohistochemistry staining was performed on 276 meningioma samples from Sun Yat-sen University Cancer Center. Expression levels of EZH2, H3K27me3, Ki67, programmed cell death protein 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), CD4, CD8, CD20, FOXP3, CD68, and CD163 were evaluated. Cox regression analyses were performed, and the Kaplan-Meier (KM) method was used to construct survival curves. In addition, we use biological information methods to analyze the mRNA expression of EZH2 and its relationship with the prognosis and immune microenvironment in the gene expression omnibus (GEO) database.
Enhancer of zeste homolog 2 expression is concentrated in World Health Organization (WHO) grades 2 and 3 meningiomas (8.3+ and 33.3%+). We found that EZH2 expression was associated with a worse prognosis in meningioma ( < 0.001), the same results were confirmed in the GEO database ( < 0.001). Both EZH2 expression and H3K27me3 deletion ( = 0.035) predicted a worse prognosis, but EZH2 has no correlation with H3K27me3 expression. EZH2 expression was closely associated with increased Ki67 index ( < 0.001). In addition, EZH2 was associated with the immune microenvironment and positively correlated with PD-L1 expression ( < 0.001).
Enhancer of zeste homolog 2 is a new prognostic biomarker in meningioma. It correlates with PD-L1 expression and closely related to tumor immunosuppression. Our research can provide a reference for the potential targeted therapy and immunotherapy of meningioma in the future.
zeste同源物2增强子（EZH2）是一种重要的表观遗传调节因子，主要通过组蛋白甲基转移酶调节组蛋白H3赖氨酸27三甲基化（H3K27me3），并参与促进肿瘤的发展。目前，脑膜瘤中H3K27me3表达缺失是一个不良预后因素，但EZH2在脑膜瘤中的研究较少。因此，我们旨在探讨EZH2在脑膜瘤中的表达及其与预后和免疫微环境的相关性，为随后脑膜瘤潜在的靶向治疗和免疫治疗奠定基础。
对中山大学肿瘤防治中心的276例脑膜瘤样本进行组织芯片免疫组化染色。评估EZH2、H3K27me3、Ki67、程序性细胞死亡蛋白1（PD-1）、程序性细胞死亡1配体1（PD-L1）、CD4、CD8、CD20、FOXP3、CD68和CD163的表达水平。进行Cox回归分析，并采用Kaplan-Meier（KM）法构建生存曲线。此外，我们使用生物信息学方法分析基因表达综合数据库（GEO）中EZH2的mRNA表达及其与预后和免疫微环境的关系。
zeste同源物2增强子的表达集中在世界卫生组织（WHO）2级和3级脑膜瘤中（分别为8.3%+和33.3%+）。我们发现EZH2表达与脑膜瘤预后较差相关（<0.001），在GEO数据库中也证实了相同的结果（<0.001）。EZH2表达和H3K27me3缺失均预测预后较差（=0.035），但EZH2与H3K27me3表达无相关性。EZH2表达与Ki67指数升高密切相关（<0.001）。此外，EZH2与免疫微环境相关，与PD-L1表达呈正相关（<0.001）。
zeste同源物2增强子是脑膜瘤中的一种新的预后生物标志物。它与PD-L1表达相关，与肿瘤免疫抑制密切相关。我们的研究可为未来脑膜瘤的潜在靶向治疗和免疫治疗提供参考。
