Transcriptome analysis reveals differences in cell cycle, growth and migration related genes that distinguish fibroblasts derived from pre-invasive and invasive breast cancer.
As the most common form of pre-invasive breast cancer, ductal carcinoma in situ (DCIS) affects over 50,000 women in the US annually. Despite standardized treatment involving lumpectomy and radiation therapy, up to 25 % of patients with DCIS experience disease recurrence often with invasive ductal carcinoma (IDC), indicating that a subset of patients may be under-treated. As most DCIS cases will not progress to invasion, many patients may experience over-treatment. By understanding the underlying processes associated with DCIS to IDC progression, we can identify new biomarkers to determine which DCIS cases may become invasive and improve treatment for patients. Accumulation of fibroblasts in IDC is associated with disease progression and reduced survival. While fibroblasts have been detected in DCIS, little is understood about their role in DCIS progression.We sought to determine whether DCIS fibroblasts were similar or distinct from normal and IDC fibroblasts at the transcriptome level, fibroblasts underwent transcriptome profilingthrough bulk RNA seq and pathway analysis.  DCIS fibroblasts are phenotypically distinct from normal breast and IDC fibroblasts, and play an important role in breast cancer growth, invasion, and recruitment of myeloid cells. These studies provide novel insight into the role of DCIS fibroblasts in breast cancer progression and identify some key biomarkers associated with DCIS progression to IDC, with important clinical implications. Overall design: Fibroblasts were isolated from normal breast, DCIS and IDC tissues and were subject to bulk RNA seq. Differential gene expression analysis was conducted on DCIS fibroblast vs. normal fibroblast, DCIS fibroblast vs. IDC fibroblast and IDC fibroblast vs. normal fibroblast. Genes were validated by RT-PCR. Data were subject to pathway enrichment analysis and network analysis.