Expression pattern of m⁶A regulators is significantly correlated with malignancy and antitumor immune response of...

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.