N6-Methyladenosine Regulators Are Involved in the Progression of and Have Clinical Impact on Breast Cancer

BACKGROUND: N6-methyladenosine (m(6)A) modification has been widely studied in various cancers, and m(6)A regulators, such as METTL3, METTL14, WTAP, and YTHDF1, play crucial roles in breast cancer. However, a comprehensive study of m(6)A regulators in breast cancer is still lacking. MATERIAL/METHODS: Expression data of m(6)A regulators and clinicopathological information were acquired from The Cancer Genome Atlas (TCGA) program. Protein interaction was collected from the STRING database. Data on tumor purity and correlation among m(6)A regulators were obtained from the TIMER database. LASSO, consensus clustering, and gene set enrichment analysis (GSEA) were used to evaluate the role of m(6)A regulators. Moreover, the prognostic value of m(6)A-related genomic targets in breast cancer was analyzed by Kaplan-Meier analysis and Cox regression models. RESULTS: We found most m(6)A regulators were associated with key clinicopathological parameters, such as tumor staging, Nottingham prognostic index (NPI), and cellularity. Also, consensus clustering analysis-based grouping could effectively predict patients’ overall survival. Correlation analysis also showed that these regulators interacted with each other. Patients were further split into a high-risk group and low-risk group based on Cox and LASSO analysis. High-risk patients had a significantly worse overall survival than did low-risk patients. Moreover, AKT1 and MYC were enriched in patients in the high-risk group, according to GSEA analysis. The patients in the high-risk group also displayed resistance to chemoradiotherapy or hormone therapy. CONCLUSIONS: The m(6)A regulators are critical participants in the development and progression of breast cancer and are likely to be used to predict prognosis and develop treatment strategies.