Effect of N6-methyladenosine (m6A) regulator-related immunogenes on the prognosis and immune microenvironment of breast cancer

BACKGROUND: Breast cancer is one of the most common malignant tumor and the prognosis remains unsatisfying. Various studies demonstrate that m6A modulators are new predictors of prognosis in immune microenvironment. We aimed to identify several m6A regulator-related immunogenes and explore the relationship between m6A regulator-related immunogenes and breast cancer prognosis as well as the tumor immune microenvironment (TIME). METHODS: RNA sequencing data and clinical information on 21 m6A regulators in 1,047 breast cancer samples were downloaded from The Cancer Genome Atlas (TCGA), and immune gene data were downloaded from InnateDB. Kaplan-Meier survival analysis was conducted with log-rank test using the survival package. An m6A-related immunogene-prognostic signature was then constructed, followed by immune infiltration and checkpoint analyses. RESULTS: A risk prognostic signature of m6A regulator-related immunogenes, including TOX, PSME2, MCTS1, NFKBIE, SH3BP4, RSPH1, JAK1, MLLT4, and PTGES3, was constructed. Furthermore, univariate and multivariate Cox regression analyses suggested that the tumor stage and risk score could be independent prognostic factors for patients with breast cancer. Immune infiltration analysis showed that the infiltration levels of T cells, memory B cells, activated NK cells, and macrophages between the high- and low-risk groups were significantly different. In addition, checkpoint analyses demonstrated that the levels of immune checkpoint genes, such as those of LAG3, PDCD1, CTLA4, and HAVCR2, were downregulated in the high-risk group compared to those in the low-risk group. CONCLUSIONS: Our findings suggest that the m6A regulator-related risk prognostic signature can predict the prognosis of breast cancer and that it is related to the immune microenvironment.