Abstract
BACKGROUND: Breast cancer is a heterogeneous malignancy with diverse tumor subpopulations and complex tumor-immune interactions. This study explores the prognostic and functional roles of PDE3B and HBB in breast cancer, focusing on their contributions to proliferation and immune microenvironment modulation. METHODS: Single-cell RNA sequencing (scRNA-seq) and TCGA data were analyzed to identify malignant subpopulations and prognostic genes. Differential gene expression, KEGG enrichment, LASSO regression, and Kaplan-Meier survival analyses were performed. Immune infiltration was assessed using EPIC deconvolution. Functional validation included qRT-PCR, IHC, Western blot, and proliferation assays in MDA-MB-231 cells. RESULTS: Malignant cell type 3 exhibited the highest proliferative potential. PDE3B and HBB were identified as prognostic markers, strongly associated with poor survival and immune cell infiltration. Overexpression of these genes enhanced proliferation, while their knockout suppressed it. CONCLUSION: PDE3B and HBB drive breast cancer proliferation and immune modulation, making them promising biomarkers and therapeutic targets. Further research should assess their potential in targeted therapies.