Expression and clinical prognostic value of m6A RNA methylation modification in breast cancer.

Background: N6-methyladenosine(m6A) methylation modification affects the tumorigenesis, progression, and metastasis of breast cancer (BC). However, the expression characteristics and prognostic value of m6A modification in BC are still unclear. We aimed to evaluate the relationship between m6A modification and clinicopathological characteristics, and to explore the underlying mechanisms.

Methods: Three public cohorts and our clinical cohort were included: 1091 BC samples and 113 normal samples from the TCGA database, 1985 BC samples from the METABRIC database, 1764 BC samples from the KM Plotter website, and 134 BC samples of our clinical cohort. We collected date from these cohorts and analyzed the genetic expression, gene-gene interactions, gene mutations, copy number variations (CNVs), and clinicopathological and prognostic features of 28 m6A RNA regulators in BC.

Results: This study demonstrated that some m6A regulators were significantly differenially expressed in BCs and their adjacent tissues, and also different in various molecular types. All 28 studied m6A regulators exhibited interactions. KIAA1429 had the highest mutation frequency. CNVs of m6A regulators were observed in BC patients. The expression of the m6A regulators was differentially associated with survival of BC. Higher CBLL1 expression was associated with a better prognosis in BC than lower CBLL1 expression. Functional analysis showed that CBLL1 was related to the ESR1-related pathway, apoptosis-related pathway, cell cycle pathway and immune-related pathway in BC.

Conclusions: m6A RNA modification modulated gene expression and thereby affected clinicopathological features and survival outcomes in BC. CBLL1 may be a promising prognostic biomarker for BC patients.