Integrated Transcriptomic Analysis Identifies Overlapping Gene Networks Between Breast Cancer Stem Cells and...

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Breast cancer stem cells (BCSCs) drive treatment resistance and recurrence.
• Mesenchymal stem cells (MSCs) primed with paclitaxel can activate T cells for immunotherapy.
• Molecular links between BCSCs and immune cells are not well understood.

Purpose of the Study:

• Identify shared gene networks between BCSCs, paclitaxel-treated cells, activated T cells, and paclitaxel-primed MSCs.
• Validate the functional relevance of these networks in targeting BCSCs.

Main Methods:

• Comparative transcriptomic analysis of TCGA data.
• Protein-protein interaction (PPI) network analysis, Gene Ontology (GO) enrichment, and KEGG pathway mapping.
• Experimental validation using MTT assays and qRT-PCR.

Main Results:

• Identified 158 co-expressed genes forming a network with TP53, AKT1, and STAT3 as key hubs.
• TP53 mutations correlated with poor prognosis.
• Combined paclitaxel and T-cell treatment reduced BCSC viability by 75% and modulated TP53 and PIK3CA pathways.

Conclusions:

• TP53, AKT1, and STAT3 are critical therapeutic targets connecting BCSCs and immune activation.
• Paclitaxel-primed MSC-activated T cells synergize with chemotherapy to suppress BCSC viability.
• This provides a rationale for combinatorial immunotherapy in breast cancer.