The Association Between The Expression Of Transcriptor FOXC1and The Triple Negative Breast Cancer

Background:Breast cancer is the leading cause of malignancy-related mortality in women worldwide. And triple-negative breast cancer has become a key research point recently, due to its specific biological characteristics and poor prognosis. Transcription factors are a group of modular proteins which are involved in a wide variety of biological processes of development, differentiation and metabolism through regulating their target genes. Transcription factor FOXC1is a member of Forkhead box family, and it participates in the human growth, development and metabolism. The gene mutation or abnormal expression of FOXC1may lead to many kinds of diseases, as well play an important role in the occurrence and progression of tumors. It is confirmed that FOXC1is expressed strongly and predicts poor prognosis specific in basal-like breast cancer, which shares striking similarities with TNBC.Purpose:To investigate the expression of FOXC1in TNBC, prove the relationship between the FOXC1and TNBC, and analyze the role of FOXC1with clinicopathological and prognostic factors, according to the follow-up data. It also have the poteintial of discovering the tumor biomarker for TNBC/BLBC, revealing the mechanism of tumor occurrence, progression and metastasis, and providing prognostic indicator or treatment target.Methods:47patients with primary breast cancer who underwent surgical resection at PUMCH were followed up. The study included paraffin embedded tissue of47patients with primary lesions. The patients are divided into two groups: experienmental group with recurrence or metastasis and control group without recurrence or metastasis.(1) Immunohistochemistry technique was adopted to detect the expression of FOXC1in47paraffin embedded TNBC tissues. The comparism of the expression of FOXC1in the two groups, and the correlation between the expression of FOXC1and the clinicopathologic features were statistically analyzed.(2) Disease-free survival rate and overall survival rate was described by the life table method and Kaplan-Meier estimate. The Log-Rank test was used to compare DFS curves or OS curves.(3) A multivariate proportional hazard model (Cox model) was used to test the prognostic effect of all factors on study. All data were analyzed in SPSS software version20.0.Results:(1) In paraffin embedded tissues, the positively expressed FOXC1protein was located in nucleus and/or cytoplasm of TNBC cell. The expression rate of FOXC1in all TNBC samples is48.9%(23/47), which are68.2%(15/22) and32.0%(8/25) seperately in the experienmental group and the control group (P<0.05). The expression of FOXC1had no relationship with age, histological type, histological grade, tumor size, number of positive LNs, lymphovascular invasion, p53expression, Ki-67index or AJCC clinical stage (P>0.05).(2) In univariate Kaplan-Meier analysis, the expression of FOXC1was associated with poor disease-free survival, and the age was associated with poor overall survival in TNBC patients (P<0.05).(3) In multivariate Cox analysis, the expression of FOXC1was independent prognostic factor of DFS, and the number of positive LNs and the expression of FOXC1were independent prognostic factors of OS in TNBC patients(.P<0.05).Conclusion:(1) The expression rate of FOXC1in TNBC was48.9%(23/47) in this study.(2) The expression level of FOXC1in the experienmental group was significantly higher than those in the control group.(3) The expression of FOXC1was independent prognostic factor of DFS/recurrence or metastasis in TNBC patients.(4) The number of positive LNs and the expression of FOXC1were independent prognostic factor of OS in TNBC patients.