Medical Oncology Department, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangdong, Guangzhou, China.
Medicine (Baltimore). 2024 Apr 26;103(17):e37950. doi: 10.1097/MD.0000000000037950.
N6-methyladenosine (m6A) is the most common modification on RNAs and LncRNAs. It plays an important role in cancer stem cell differentiation, T cell differentiation, and immune homeostasis. In this study, we explored the potential roles of m6A modification of RNA in melanoma and investigated the immune cell infiltration in tumor microenvironment in diverse m6Aclusters and different m6Ascore groups. A consensus clustering algorithm determined m6A modification patterns based on 14 m6A regulators, and further explored the biological functions and the connection with TME. An m6A-related gene signature (m6Ascore) was constructed based on m6A-related genes using principal component analysis. Three m6A modification patterns were identified based on 14 m6A regulators, named as m6Aclusters A-C. The prognosis of m6Acluster A was more favorable than m6Aclusters B and C, and it was more closely associated with immune regulation. To quantify the m6A modification patterns of individual tumor, an m6Ascore was constructed, and patients were classified into high and low m6Ascore groups. The low m6Ascore group, which had a favorable prognosis, was more relevant to immunology. The expression of PD-L1 was higher and the immunophenoscore (IPS) revealed stronger response to immunotherapy in the low m6Ascore group. This study identified 3 m6A modification patterns with different immune characteristics and constructed an m6Ascore system to predict prognosis and immunogenicity of patients, which is conducive to clinical prognosis judgment and individual treatment.
N6-甲基腺苷（m6A）是 RNA 和 LncRNA 上最常见的修饰。它在癌症干细胞分化、T 细胞分化和免疫稳态中发挥重要作用。在这项研究中，我们探索了 RNA 的 m6A 修饰在黑色素瘤中的潜在作用，并研究了不同 m6A 聚类和不同 m6A 评分组中肿瘤微环境中的免疫细胞浸润。共识聚类算法基于 14 个 m6A 调节剂确定了 m6A 修饰模式，并进一步探索了它们与 TME 的生物学功能和联系。基于 m6A 相关基因使用主成分分析构建了 m6A 相关基因特征（m6Ascore）。基于 14 个 m6A 调节剂确定了三种 m6A 修饰模式，分别命名为 m6Acluster A-C。m6Acluster A 的预后优于 m6Acluster B 和 C，与免疫调节的关系更为密切。为了量化个体肿瘤的 m6A 修饰模式，构建了 m6Ascore，并将患者分为高 m6Ascore 组和低 m6Ascore 组。低 m6Ascore 组预后较好，与免疫学相关性更强。低 m6Ascore 组的 PD-L1 表达更高，免疫表型评分（IPS）显示对免疫治疗的反应更强。本研究确定了具有不同免疫特征的 3 种 m6A 修饰模式，并构建了 m6Ascore 系统来预测患者的预后和免疫原性，有助于临床预后判断和个体化治疗。
