Comprehensive Analysis of m6A Regulators Identifies YTHDF3 as a Promising Prognostic Biomarker for Breast Cancer.

Abstract

The expression landscape and prognostic value of N6-methyladenosine (m6A)-related genes remain largely uncharacterized in breast cancer. Here, we performed an integrative analysis of their expression profiles and clinical relevance. Utilizing multi-omics datasets and experimental validation, we conducted a systematic investigation of m6A-related genes in breast cancer. These genes exhibited pronounced differential expression in breast cancer, yet their correlation with molecular features such as promoter methylation and copy number alterations was limited. Univariate survival analysis indicated that aberrant expression of RBM15B, METTL16, HNRNPC, YTHDF1, YTHDF3, and IGF2BP1 was significantly linked to patient prognosis. Multivariate Cox regression further identified elevated YTHDF3 expression as an independent prognostic factor. Functional network analysis indicated YTHDF3 is potentially involved not only in RNA processing and metabolism but also in DNA repair, pri-miRNA processing, telomere stability, and immune infiltration. Moreover, upregulation of YTHDF3 mRNA was confirmed in clinical breast cancer specimens. Collectively, m6A-related genes are dysregulated in breast cancer and correlate with patient outcomes, highlighting their biomarker potential, with YTHDF3 warranting in-depth investigation.