The Role Of FOXC1 In Epithelial-mesenchymal Transition In Epithelial Ovarian Cancer

Research BackgroundOvarian cancer is one of the most common female malignancies in the world.It is very important to control the invasion and metastasis of cancer cells.It is difficult to study the clinical diagnosis and treatment of ovarian cancer.Epithelial transformation is epithelial cells gradually lose their characteristic cell polarity and intercellular connection,so as to obtain interstitial cells with the invasion and migration ability of the process.Epithelial transformation is involved in the initiation of invasion and metastasis of epithelial tumors,leading to the spread of tumor cells from the original site to the distal,in the process of invasion and metastasis of malignant tumors play a major pathological role.In vivo and in vitro studies have shown that EMT-related molecules not only in epithelial ovarian cancer can promote and maintain the tumor microenvironment,for tumor development and metastasis to provide more favorable conditions,but also involved in epithelial ovarian cancer chemotherapy drug resistance occur.Transcription factor FOXC1 as a member of the FOX family,early detection of its main and Axenfeld-Rieger syndrome,the current study confirmed FOXC1 and tumor epithelial transformation and tumor metastasis is closely related to the disease as a new biomarker,But also for clinical diagnosis and treatment to provide new targets.At present,FOXC1 in the development of epithelial ovarian cancer,invasion and metastasis mechanism in the absence of further study.This study was divided into two parts to study the role of transcription factor FOXC1 in epithelial mesenchymal transition of ovarian cancer.ObjectiveTo investigate the expression of FOXC1,E-cadherin and Vimentin in epithelial ovarian tumors,and to explore the relationship between FOXC1 and clinicopathological features of epithelial ovarian cancer and the correlation between E-cadherin and Vimentin protein expression,and to investigate the relationship between FOXC1 and epithelial ovarian cancer The 3-year cumulative survival rate of FOXC1,E-cadherin and Vimentin in ovarian cancer tissues.The expression of FOXC1,E-cadherin and Vimentin protein and mRNA were detected by using FOXC1 overexpressing SKOV3 ovarian cancer cell line in this study group to explore the role of FOXC1 gene in epithelial ovarian epithelial transformation.MethodThirty cases of benign epithelial ovarian tumors,30 cases of borderline epithelial ovarian tumors and 70 cases of epithelial ovarian cancer were detected by immunohistochemical SP method.The expression of FOXC1,E-cadherin and Vimentin were detected and compared with the patients The 3-year cumulative survival rates of FOXC1,E-cadherin and Vimentin differences were analyzed by correlation and clinical and pathological parameters.In this study group,the ovarian cancer cell SKOV3 lentivirus stabilizer was established: FOXC1 overexpression group,FOXC1 overexpression negative control group and blank control group.The expression of FOXC1,E-cadherin and Vimentin protein in SKOV3 cells were detected by Western-blot.The expression of FOXC1,E-cadherin and Vimentin protein in SKOV3 cells before and after transfection were analyzed by qRT-PCR The expression of FOXC1,E-cadherin and Vimentin mRNA in SKOV3 cells before and after transfection were analyzed.ResultThe positive expression rates of FOXC1 protein in epithelial ovarian cancer,borderline epithelial ovarian tumor and benign epithelial ovarian tumor were 40%,46% and 76% respectively,the difference was statistically significant(P <0.05).In the epithelial ovarian cancer tissues,20 cases of E-cadherin were positive in 28 cases of FOXC1-positive ovarian cancer tissues,and 11 cases were positive in E-cadherin expression in 42 cases of ovarian cancer tissues The results showed that FOXC1 expression was positively correlated with E-cadherin expression(r = 0.446,P = 0.000).And 28 cases of FOXC1 positive expression of ovarian cancer tissue Vimentin positive expression in 11 cases,and 42 cases of negative expression of ovarian cancer tissue Vimentin positive expression of 29 cases,the correlation analysis results suggest that FOXC1 expression and Vimentin expression was negatively correlated R =-0.295,P = 0.014).The low expression of FOXC1 protein in epithelial ovarian cancer group was correlated with the clinical stage of tumor,poor degree of differentiation and lymph node metastasis(P <0.05).The 3-year cumulative survival rate of FOXC1 and E-cadherin positive patients was 82.1% and 80.6%,which was higher than that of FOXC1 and E-cadherinnegative patients 69.0% and 69.2% respectively.The 3-year cumulative survival rate of Vimemtin positive patients Was 70% lower than 80% of Vimemtin-negative patients(P <0.05).The expression of FOXC1 and E-cadherin in FOXC1 overexpression group was significantly higher than that in normal control group and negative control group(P <0.05).The expression of Vimentin protein in FOXC1 overexpression group was significantly higher than that in control group MRNA expression was significantly lower than that in normal control group and negative control group(P <0.05).ConclusionThe expression of FOXC1 protein was down-regulated in epithelial ovarian cancer tissues,suggesting that FOXC1 expression was associated with the occurrence of ovarian cancer.2.The expression of FOXC1 in ovarian cancer tissues was down-regulated simultaneously with epithelial markersE-cadherin expression was down-regulated,and the expression of Vimemtin was up-regulated,suggesting that FOXC1 expression may be involved in the development of epithelial ovarian transformation of epithelial ovarian cancer.The expression of FOXC1,E-cadherin and Vimentin overexpression in ovarian cancer were correlated with the clinical stage of epithelial ovarian cancer,poor differentiation and lymph node metastasis,suggesting that FOXC1 may be associated with epithelial ovarian epithelial transformation and development related.The expression of FOXC1 and E-cadherin in human ovarian cancer SKOV3 cells was increased and the expression of Vimentin was decreased,suggesting that FOXC1 expression was involved in the epithelial transformation of epithelial ovarian cancer.