Abstract:
Objective To investigate the correlation of fatty acid synthase (FASN) expression with the clinicopathological features and prognosis of invasive micropapillary carcinoma (IMPC) of the breast.
Methods 105 cases of breast IMPC patients and 105 cases of invasive ductal carcinoma-no special type (IDC-NOS) patients that were admitted to Tianjin Medical University Cancer Institute & Hospital between the period of January 2010 to December 2015 were selected, and FASN immunohistochemical staining was performed for statistical analysis. The effects of FASN on the proliferation and migration of T47D breast cancer cells were investigated by CCK8 and scratch experiments. Changes in the Wnt/β-catenin signaling pathway and epithelial-mesenchymal transition (EMT) key proteins owing to FASN were assessed using Western blot.
Results The expression of FASN in IMPC (61.0%, 64/105) was significantly higher than that in IDC-NOS (31.4%, 33/105), and the difference was statistically significant (P<0.001). Its expression in IMPC patients was positively correlated with vascular tumor thrombus, N stage, and Ki-67 expression (P<0.05) and negatively correlated with disease-free survival (DFS) and overall survival (OS) period (P<0.01). The high expression of FASN was an independent risk factor for the decreased DFS and OS in IMPC patients (P<0.05). The proliferation and migration ability of T47D breast cancer cells were significantly decreased after the knockdown of FASN (P<0.001). FASN promoted the Wnt/β-catenin signaling pathway and EMT in T47D breast cancer cells.
Conclusions FASN promotes EMT through Wnt/β-catenin signaling pathway, leading to the proliferation and migration of T47D breast cancer cells. The high expression of FASN is positively correlated with clinicopathological factors such as high invasion and metastasis of IMPC, and it is an independent risk factor for predicting the prognosis of IMPC patients.