Abstract
BACKGROUND: Ductal carcinoma in situ (DCIS) is a precursor to breast cancer. The mechanisms by which the stroma of DCIS affects disease progression remain elusive. Thus, the aim of this study is to identify key stroma genes that affect DCIS progression and to define high-risk DCIS cases. METHOD: Gene expression matrix files from the Gene Expression Omnibus (GEO) database were selected to identify candidate genes associated with the stromal transition from DCIS to invasive ductal carcinoma (IDC). An integrative approach was employed to identify and functionally characterize driver genes of DCIS progression. In vitro experiments were performed to validate the role of these genes. RESULTS: We identified 13 differentially expressed genes (DEGs), of which 5 were selected as candidate drivers. Gene set enrichment analysis (GSEA) revealed the biological functions of RAMP2 and ADM2, while in vitro functional assays demonstrated that ADM2 knockdown and RAMP2 overexpression in breast cancer cell lines significantly suppressed cellular proliferation and invasion. CONCLUSION: This study identified and validated the roles and functions of ADM2 and RAMP2 and revealed their function as key driver genes in the progression of ductal carcinoma in situ (DCIS). Collectively, our findings elucidate critical genetic mechanisms underlying DCIS progression and provide novel insights for the development of personalized therapeutic strategies.