Decoding the Tumor Microenvironment of Myoepithelial Cells in Triple-Negative Breast Cancer Through Single-Cell and...

Area of Science:

• Oncology
• Genomics
• Immunology

Background:

• Triple-negative breast cancer (TNBC) is aggressive with limited treatment options.
• Myoepithelial cells (MECs) within the tumor microenvironment may influence TNBC progression.
• Novel therapeutic strategies are urgently needed for TNBC.

Purpose of the Study:

• To investigate gene expression and genomic alterations in MECs from TNBC tissues.
• To develop and validate a prognostic model for TNBC patient survival.
• To identify potential therapeutic targets for TNBC.

Main Methods:

• Single-cell RNA sequencing of MECs from normal and TNBC tissues.
• Copy number variation, pseudotime, and CoxBoost prognostic modeling.
• Mendelian randomization and siRNA knockdown for TPD52 validation.

Main Results:

• TNBC MECs exhibit altered proliferation, immune, inflammatory, and extracellular matrix gene expression.
• The prognostic model accurately predicted patient survival and identified high-risk groups.
• TPD52 was identified as a tumor-promoting gene; its knockdown inhibited TNBC cell proliferation and migration.

Conclusions:

• MECs play a significant role in TNBC progression.
• A validated CoxBoost model aids personalized TNBC treatment strategies.
• TPD52 represents a potential therapeutic target for TNBC intervention.