A Prognostic Gene Signature and Subtype-Specific Drug Sensitivity in TNBC Revealed by Single-Cell and Bulk RNA Sequencing: Insights into Stemness and Tumor Heterogeneity

Triple-negative breast cancer (TNBC) remains one of the most aggressive and therapeutically challenging breast cancer subtypes due to its lack of targetable receptors and intrinsic chemoresistance. This study applies integrated multi-omics approaches combining single-cell RNA sequencing (scRNA-seq) with bulk transcriptomic and clinical data to investigate cellular heterogeneity and underlying mechanisms of drug resistance in TNBC. Analysis of the scRNA-seq dataset (GSE176078) reveals tumor microenvironment diversity and identifies distinct cell populations contributing to tumor progression and treatment resistance. Unsupervised clustering of TCGA-BRCA data delineates three molecular subtypes with unique biological and metabolic profiles. Differential gene expression analysis identifies key genes associated with prognosis and drug response. A prognostic gene signature composed of selected differentially expressed genes is developed and validated across independent cohorts, demonstrating robust predictive performance. The findings provide critical insights into TNBC heterogeneity and offer a foundation for personalized therapeutic strategies.