DNM3 Expression In Breast Carcinoma-associated Fibroblasts And Its Prognosis In Triple-negative Breast Cancer

As one of major component in breast cancer microenviroment, breast cancer-associated fibroblasts take an important role in the tumorgenesis, local invasion, metastasis and therapeutic intolerance of breast cancer. Cacinoma-associated fibroblast (CAFs) can be tranformed from normal fibroblasts (NFs) in vivo. CAFs and NFs can be differentiated with each other according to the morphological change and expression of a-smooth muscle actin (a-SMA). Our study includes the three major parts as follows: First, the supernate of triple-negative breast cancer (TNBC) cell lines (MDA-MB-231 and MDA-MB-468) was used to induce NFs to transform to CAFs which expressed a-SMA both on mRNA and protein level, thus creating CAFs and NFs in vitro. Then, Affymetrix HumanU133plus2.0 microarray was applied to screen the different biomarkers between CAFs and NFs; meanwhile 5 pairs of human breast cancer tissues and related normal tissues were microdissected to get CAFs and NFs in vivo. RNA was extracted to verify the screening results. Last, DNM3, regarded as the target gene after screening, was further studied. DNM3 expression in the carcinomatous component of TNBC had no impact on the disease-free survival (DFS)(p=0.58) and overall survival (OS) (p=0.87) according to Kaplan-Meier Plotter online. On the other hand, TNBC tissues (n=79) were collected in the Fudan University Shanghai Cancer Center to evaluate DNM3 expressioin via immunohistochemistry (IHC) and make the related survival analysis. High DNM3 expression in the stromal part of TNBC was related to poor DFS (HR 8.359; 95%CI 2.941-23.756; p=0.001) and OS(HR 5.743; 1.709-19.294; p=0.005). So, it can be concluded that DNM3 expression in stromal component of TNBC was associated with poor prognosis of breast cancer while its expression in carcinomatous component was not.