In addition, we found using Bayesian network-based machine learning that 30 NRF1 motif-enriched genes including growth factor receptors-FGFR1, IGF1R; E2Fs transcription factor family-E2F1, E2F3; MAPK pathway-SHC2, GRB2, MAPK1; PI3K-AKT-mTOR signaling pathway-PIK3CD, PIK3R1, PIK3R3, RPS6KB2; WNT signaling pathway-WNT7B, DLV1, DLV2, GSK3B, NRF1, and DDB2, known for its role in DNA repair and involvement in early events associated with metastatic progression of breast cancer cells, were associated with HER2-amplified breast cancer.
Taken together, our findings enlighten understanding of how breast cancer cells progress to an invasive phenotype and underscore potential clinical interest in DDB2 as a prognostic marker or therapeutic target in this setting.
For the first time, these data give supporting evidence that DDB2 is a new transcriptional regulator, and they provide insight into the molecular function of breast cancer cell growth, which will have an important clinical interest.