More than 24 regulators have been revealed to dynamically participant in N6-methyladenosine (m⁶A) RNA methylation, and play critical roles in tumorigenesis and development of cancers. However, their functional roles have not been comprehensively clarified in breast cancer. Here we systematically analyzed the RNA sequencing data of 24 main m⁶A RNA methylation regulators in 775 breast cancer patients from The Cancer Genome Atlas dataset. Consensus clustering of the 24 m⁶A regulators was carried out and identified two patient subgroups, RNA methylation 1/2 (RM1/2). RM1 demonstrated generally lower RNA methylation modification than that of RM2, and had significantly shorter overall survival. The hallmarks of PI3K/AKT signaling in cancer, KRAS signaling and angiogenesis were significantly enriched in RM1. Moreover, the association between m⁶A regulators and antitumor immune response was also investigated in this study and revealed that RM2 was associated with significantly higher expressions of HLA-A, higher numbers of tumor-infiltrating CD8⁺ T cells, helper T cells and activated NK cells, but lower expressions of PD-L1, PD-L2, TIM3, and CCR4 than RM1. In conclusion, the expression pattern of m⁶A regulators was significantly correlated with the malignancy, prognosis and antitumor immune response in breast cancer, which might serve as potential targets and biomarkers for immunotherapy.

已发现超过 24 种调节剂动态参与 N6-甲基腺苷 (m ⁶ A) RNA 甲基化，并在肿瘤发生和癌症发展中发挥关键作用。然而，它们在乳腺癌中的功能作用尚未得到全面阐明。在这里，我们系统地分析了来自癌症基因组图谱数据集的 775 名乳腺癌患者的 24 个主要 m ⁶ A RNA 甲基化调节因子的 RNA 测序数据。24 m ^{6 的}共识聚类进行了调节并确定了两个患者亚组，即 RNA 甲基化 1/2 (RM1/2)。RM1 的 RNA 甲基化修饰通常比 RM2 低，并且总生存期显着缩短。PI3K/AKT 信号在癌症中的标志、KRAS 信号和血管生成在 RM1 中显着富集。此外，本研究还研究了m ⁶ A 调节因子与抗肿瘤免疫反应之间的关联，结果表明 RM2 与 HLA-A 的显着更高表达、更高数量的肿瘤浸润 CD8 ⁺ T 细胞、辅助 T 细胞和活化NK 细胞，但 PD-L1、PD-L2、TIM3 和 CCR4 的表达低于 RM1。综上所述，m ⁶的表达模式A调节因子与乳腺癌的恶性程度、预后和抗肿瘤免疫反应显着相关，可作为免疫治疗的潜在靶点和生物标志物。