Objective:

To investigate the role of lactylation in the breast cancer tumor microenvironment and its clinical significance, particularly as a potential prognostic biomarker, through single-cell analysis and the development of a prognostic model.

Key Findings:

• Lactylation-related transcriptional activity was highest in epithelial cells, particularly in TNBC, suggesting a critical role in tumor biology.
• Elevated lactylation states correlated with immune response pathways and a partially immune-suppressive microenvironment, indicating potential therapeutic targets.
• The 14-gene signature effectively classified patients into distinct prognostic categories, which may guide treatment decisions.
• High-risk tumors exhibited unique immune and stromal profiles, highlighting the heterogeneity of breast cancer.

Interpretation:

The study identifies lactylation as a significant factor in breast cancer heterogeneity and patient outcomes, suggesting its potential as a prognostic biomarker.

Limitations:

• The lactylation score serves as an indirect proxy rather than a direct measurement of lactylation, which may affect the accuracy of the findings.
• Further mechanistic and clinical validation is required to confirm findings and their applicability in clinical settings.

Conclusion:

The research highlights the importance of lactylation in breast cancer and proposes a transcriptome-centric framework for risk assessment, necessitating further validation to ensure reliability.