Shi Aiai, Lin Chaohuan, Wang Jilu, Chen Ying'ao, Zhong Jinjin, Lyu Jie
Joint Centre of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, People's Republic of China.
Joint Centre of Translational Medicine, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325001, People's Republic of China.
Mol Ther Nucleic Acids. 2023 Dec 13;35(1):102100. doi: 10.1016/j.omtn.2023.102100. eCollection 2024 Mar 12.
Epigenetic regulation contributes to the dysregulation of gene expression involved in cancer biology. Nevertheless, the roles of epigenetic regulators (ERs) in tumor immunity and immune response remain basically unclear. Here, we developed the epigenetic regulator in immunology (EPRIM) approach to identify immune-related ERs and comprehensively dissected the ER regulation in tumor immune response across 33 cancers. The identified immune-related ERs were related to immune infiltration and could stratify cancer patients into two risk groups in multiple independent datasets. These patient groups were characterized by distinct immune functions, immune infiltrates, driver gene mutations, and prognoses. Furthermore, we constructed an immune ER-based signature and highlighted its potential utility in predicting clinical benefit from immunotherapy and selecting therapeutic agents. Taken together, our identification and evaluation of immune-related ERs highlight the usefulness of EPRIM for the understanding of ERs in immune regulation and the clinical relevance in evaluation of cancer patient prognosis and response to immune checkpoint blockade therapy.
表观遗传调控导致了癌症生物学中涉及的基因表达失调。然而，表观遗传调节因子（ERs）在肿瘤免疫和免疫反应中的作用仍基本不清楚。在此，我们开发了免疫学中的表观遗传调节因子（EPRIM）方法来识别免疫相关的ERs，并全面剖析了33种癌症中肿瘤免疫反应中的ER调控。所鉴定的免疫相关ERs与免疫浸润相关，并且可以在多个独立数据集中将癌症患者分为两个风险组。这些患者组具有不同的免疫功能、免疫浸润、驱动基因突变和预后特征。此外，我们构建了基于免疫ER的特征，并强调了其在预测免疫治疗的临床益处和选择治疗药物方面的潜在效用。综上所述，我们对免疫相关ERs的识别和评估突出了EPRIM在理解免疫调节中的ERs以及评估癌症患者预后和对免疫检查点阻断治疗反应的临床相关性方面的有用性。
