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Personalized treatment decision-making using a machine learning-derived lactylation signature for breast cancer prognosis.


ABSTRACT:

Background

Breast cancer is a heterogeneous malignancy with complex molecular characteristics, making accurate prognostication and treatment stratification particularly challenging. Emerging evidence suggests that lactylation, a novel post-translational modification, plays a crucial role in tumor progression and immune modulation.

Methods

To address breast cancer heterogeneity, we developed a machine learning-derived lactylation signature (MLLS) using lactylation-related genes selected through random survival forest (RSF) and univariate Cox regression analyses. A total of 108 algorithmic combinations were applied across multiple datasets to construct and validate the model. Immune microenvironment characteristics were analyzed using multiple immune infiltration algorithms. Computational drug-repurposing analyses were conducted to identify potential therapeutic agents for high-risk patients.

Results

The MLLS effectively stratified patients into low- and high-risk groups with significantly different prognoses. The model demonstrated robust predictive power across multiple cohorts. Immune infiltration analysis revealed that the low-risk group exhibited higher levels of immune checkpoints (e.g., PD-1, PD-L1) and greater infiltration of B cells, CD4+ T cells, and CD8+ T cells, suggesting better responsiveness to immunotherapy. In contrast, the high-risk group showed immune suppression features associated with poor prognosis. Methotrexate was computationally predicted as a potential therapeutic candidate for high-risk patients, although experimental validation remains necessary.

Conclusion

The MLLS represents a promising prognostic biomarker and may support personalized treatment strategies in breast cancer, particularly for identifying candidates who may benefit from immunotherapy.

SUBMITTER: Min S 

PROVIDER: S-EPMC12095166 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature

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Publications

Personalized treatment decision-making using a machine learning-derived lactylation signature for breast cancer prognosis.

Min Simin S   Zhang Xiaonan X   Liu Yuling Y   Wang Weiqiang W   Guan Jingwen J   Chen Yuyan Y   Sun Meng M   Wang Ziheng Z   Wang Tao T  

Frontiers in immunology 20250508


<h4>Background</h4>Breast cancer is a heterogeneous malignancy with complex molecular characteristics, making accurate prognostication and treatment stratification particularly challenging. Emerging evidence suggests that lactylation, a novel post-translational modification, plays a crucial role in tumor progression and immune modulation.<h4>Methods</h4>To address breast cancer heterogeneity, we developed a machine learning-derived lactylation signature (MLLS) using lactylation-related genes sel  ...[more]

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