N7‐Methylguanine‐Related Gene Signature Highlights EIF4E as a Novel Therapeutic Target in HER2‐Negative Breast Cancer

Globally, breast cancer remains one of the most prevalent malignancies and a leading cause of cancer‐related death in women, with over 2.3 million new cases reported annually. Despite treatment advances, one breast cancer type in particular, HER2‐negative breast cancer, lacks precise therapeutic targets. Given the role of N7‐methylguanosine (m7G) in gene regulation and its links to cancer progression, we investigated m7G regulatory gene expression and prognostic potential in HER2‐negative breast cancer. We analysed publicly available breast cancer datasets (The Cancer Genome Atlas and the Gene Expression Omnibus (GEO)) to analyse the differential expression of 14 m7G‐regulatory genes. Clustering analysis, based on m7G patterns, categorised HER2‐negative patients into two subgroups. A prognostic model was established through LASSO and Cox regression; subsequently validated by survival analysis, and further supported by functional assays confirming gene function. Our model identified CCNB1 and EIF4E as high‐risk genes, with EIF4E overexpression enhancing cell proliferation, migration and invasion. RNA‐sequencing (RNA‐seq) and pathway analyses showed that upregulated EIF4E activated Wnt signalling and extracellular matrix (ECM) components, processes required for tumour progression. High‐risk patients showed reduced immune cell infiltration and poorer survival outcomes. We highlight m7G regulatory gene potential, particularly EIF4E , as prognostic markers and therapeutic targets for HER2‐negative breast cancer. Targeting EIF4E ‐related pathways could provide new therapeutic strategies to improve breast cancer patient outcomes.