Genetic identification of the m6A-related gene YTHDF3 as a putative biomarker for breast cancer

Abstract Background Ectopic expression of m6A-related genes is a common feature in a variety of human tumors, but the expression pattern and prognostic value of these genes are poorly understood in breast cancer. This study comprehensively analyzed the expression profile of m6A-related genes and their clinical significance in breast cancer. Methods The mRNA expression of m6A-related genes was evaluated from TCGA and GTEx databases. Differences in gene amplification and DNA methylation were analyzed using cBioPortal and MethHC, respectively. Univariate and multivariate Cox survival analyses were performed based on the gene expression and clinical parameters. STRING and Metascape were used to analyze the potential molecular pathways involving these genes. Results The majority of m6A-related genes showed significantly differential expression in breast cancer tissue samples, but the correlation with molecular characteristics such as gene promoter methylation and gene amplification was weak. Univariate overall survival analysis suggested that the ectopic expression of RBM15B (p = 0.008), METTL16 (p = 0.013), HNRNPC (p = 0.01), YTHDF1 (p = 0.002), YTHDF3 (p = 0.014), and IGF2BP1 (p < 0.001) were significantly associated with prognosis. Further multivariate Cox regression survival analysis revealed that upregulation of YTHDF3 expression was an independent prognostic factor for the survival of breast cancer patients (HR: 1.024, 90%CI: 1.003–1.046, p = 0.024). This study also found that YTHDF3 was probably not only involved in the processing and metabolism of RNA, but also related to DNA repair, pri-miRNA processing, telomere stability and other important molecular pathways. Conclusions m6A-related genes are abnormally expressed in breast cancer and are associated with the prognosis of patients, indicating the potential of these genes as biomarkers for breast cancer, among which YTHDF3 requires further study.