The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China.
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
Biomolecules. 2022 Nov 2;12(11):1617. doi: 10.3390/biom12111617.
Prostate cancer (PCa) is a type of potentially fatal malignant tumor. Immunotherapy has shown a lot of potential for various types of solid tumors, but the benefits have been less impressive in PCa. Enhancer of zeste homolog 2 (EZH2) is one of the three core subunits of the polycomb repressive complex 2 that has histone methyltransferase activity, and the immune effects of EZH2 in PCa are still unclear. The purpose of this study was to explore the potential of EZH2 as a prognostic factor and an immune therapeutic biomarker for PCa, as well as the expression pattern and biological functions. All analyses in this study were based on publicly available databases, mainly containing Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), UCSCXenaShiny, and TISIDB. We performed differential expression analysis, developed a prognostic model, and explored potential associations between EZH2 and DNA methylation modifications, tumor microenvironment (TME), immune-related genes, tumor mutation burden (TMB), tumor neoantigen burden (TNB), and representative mismatch repair (MMR) genes. We also investigated the molecular and immunological characterizations of EZH2. Finally, we predicted immunotherapeutic responses based on EZH2 expression levels. We found that EZH2 was highly expressed in PCa, was associated with a poor prognosis, and may serve as an independent prognostic factor. EZH2 expression in PCa was associated with DNA methylation modifications, TME, immune-related genes, TMB, TNB, and MMR. By gene set enrichment analysis and gene set variation analysis, we found that multiple functions and pathways related to tumorigenesis, progression, and immune activation were enriched. Finally, we inferred that immunotherapy may be more effective for PCa patients with low EZH2 expression. In conclusion, our study showed that EZH2 could be a potentially efficient predictor of prognosis and immune response in PCa patients.
前列腺癌（PCa）是一种潜在致命的恶性肿瘤。免疫疗法已显示出对各种实体肿瘤的巨大潜力，但在 PCa 中的疗效却不那么显著。EZH2 是多梳抑制复合物 2 的三个核心亚基之一，具有组蛋白甲基转移酶活性，EZH2 在 PCa 中的免疫作用尚不清楚。本研究旨在探讨 EZH2 作为 PCa 预后因素和免疫治疗生物标志物的潜力，以及其表达模式和生物学功能。本研究中的所有分析均基于公共可用数据库，主要包括癌症基因组图谱（TCGA）、基因表达综合数据库（GEO）、UCSCXenaShiny 和 TISIDB。我们进行了差异表达分析，开发了预后模型，并探索了 EZH2 与 DNA 甲基化修饰、肿瘤微环境（TME）、免疫相关基因、肿瘤突变负担（TMB）、肿瘤新抗原负担（TNB）和代表性错配修复（MMR）基因之间的潜在关联。我们还研究了 EZH2 的分子和免疫学特征。最后，我们根据 EZH2 表达水平预测免疫治疗反应。我们发现 EZH2 在 PCa 中高表达，与预后不良相关，可能是独立的预后因素。EZH2 在 PCa 中的表达与 DNA 甲基化修饰、TME、免疫相关基因、TMB、TNB 和 MMR 相关。通过基因集富集分析和基因集变异分析，我们发现与肿瘤发生、进展和免疫激活相关的多个功能和途径得到了富集。最后，我们推断免疫疗法可能对 EZH2 低表达的 PCa 患者更有效。总之，我们的研究表明，EZH2 可能是 PCa 患者预后和免疫反应的潜在有效预测因子。
