Single-Cell Multiomics Integration Reveals Cell Trajectories and Regulatory Networks in Breast Cancer Progression

Background

Breast cancer is a molecularly heterogeneous disease encompassing distinct subtypes with divergent prognoses and therapeutic responses. Despite extensive bulk genomic characterization, the single-cell transcriptional trajectories, chromatin regulatory landscapes, and intercellular communication networks that drive breast cancer progression from luminal to mesenchymal states remain incompletely understood. Emerging evidence implicates gut microbiome dysbiosis as a systemic modulator of breast cancer risk, immune regulation, and treatment response; however, its coordinated characterization alongside high-resolution single-cell profiling has not been undertaken. Integrating single-cell RNA sequencing (scRNA-seq) with chromatin accessibility profiling (scATAC-seq), cell-cell communication inference, and gut microbiome 16S rRNA analysis offers a comprehensive multilayered approach to dissecting both the intratumoral regulatory logic and the systemic microbial landscape of breast cancer progression.