MYB: A potential therapeutic target in triple-negative breast cancer based on the PI3K/AKT signaling pathway.

[BACKGROUND] Compared to non-triple-negative breast cancer (Non-TNBC), triple-negative breast cancer (TNBC) exhibits significantly poorer prognosis. Previous research has confirmed that the PI3K/AKT pathway is closely associated with prognosis in breast cancer patients. Yet, it remains unclear whether this pathway is implicated in the prognostic differences observed between TNBC and Non-TNBC.

[METHODS] After downloading raw transcriptomic datasets from the GEO database and removing batch effects, we performed an integrated analysis to delineate how key genes drive the poor prognosis of TNBC. Functional enrichment, machine-learning-based feature selection, immune-cell infiltration profiling, drug-sensitivity screening, single-cell RNA sequencing and spatial transcriptomics were successively applied. Molecular-docking simulations were finally conducted to evaluate the binding affinity of MYB toward bioactive compounds derived from the Taohong Siwu Decoction.

[RESULTS] Across 113 algorithm combinations, MYB plays the most critical role in distinguishing TNBC from Non-TNBC. The constructed prognostic model confirms the significant association between MYB expression and patient outcomes. Immune cell infiltration, drug sensitivity, single-cell data analysis and spatial transcriptome revealed the specific mechanisms through which MYB influences patient prognosis. Molecular docking experiments demonstrate strong binding between key components in Taohong Siwu Decoction and MYB.

[CONCLUSION] Based on multi-omics analysis, our findings indicate that the PI3K/AKT pathway is a key factor contributing to the significant prognostic disparity between TNBC and Non-TNBC. Within this pathway, the MYB gene emerges as a potential therapeutic target. This discovery provides a potential basis for future research exploring MYB as a therapeutic target for TNBC patients.