Novel module and hub genes of distinctive breast cancer associated fibroblasts identified by weighted gene co-expression network analysis.

Abstract

As abundant and heterogeneous stromal cells in tumor microenvironment, carcinoma-associated fibroblasts (CAFs) are critically involved in cancer progression. To identify co-expression module and hub genes of distinctive breast CAFs, weighted gene co-expression network analysis (WGCNA) was conducted based on the expression array results of CAFs from seven chemo-sensitive breast cancer (BC) patients and seven chemo-resistant ones before neo-adjuvant chemotherapy. A total of 4916 genes were included in WGCNA, and 12 modules were determined. Module-trait assay showed that the blue module (cor = 0.97, P < 0.001) was associated with CAF-related chemo-resistance, which was enriched mainly as "inflammatory response", "interferon-gamma-mediated signaling" and "NIK/NF-kappaB signaling" pathways. Moreover, CXCL8, CXCL10, CXCL11, PLSCR1, RIPK2 and USP18 were found to be potentially associated with chemo-resistance related to CAFs and prognosis of BC. Our current data offered valuable insights into the molecular mechanisms of distinctive breast CAFs, which was beneficial for revealing how chemo-resistance of BC was initiated.