Expression And Clinicopathological Significance Of BRD4 And Epithelial-mesenchymal Transition Related Protein In Metastatic Breast Cancer

Objective:To explore the expression and role of BRD4 and epithelial-mesenchymal transition related proteins(Twist,E-Cadherin,Vimentin)in metastatic breast cancer.Methods:The data of patients with invasive breast cancer with complete clinical data and a clear diagnosis in the Union Hospital of Fujian Medical University from January 2010 to July 2020 were collected.Among them,119 patients with distant metastasis after operation were screened.The immunohistochemical staining method was used to detect the expression of BRD4 and epithelial-mesenchymal transition related proteins(Twist,E-Cadherin and Vimentin)in the primary and metastatic breast cancer tissues.Kendall’s tau-b correlation coefficient was used to analyze the relationship between BRD4 and epithelial-mesenchymal transition related proteins(Twist,E-Cadherin,and Vimentin).A chi-square test with multiple sample rates was used to compare BRD4,Twist,E-Cadherin,and Vimentin with age,histological grade,vascular tumor thrombus,tumor maximum diameter,lymph node metastasis,number of lymph node metastases,molecular classification,and metastasis location.,The relationship between the time of distant metastasis after operation.The differences in the expression of BRD4,Twist,E-Cadherin and Vimentin in the primary breast cancer and distant metastases were analyzed by paired chi-square test and consistency test.Results:(1)In the primary lesion,BRD4 has a positive correlation with Twist(Kendall’s tau-b=0.306,P=0.001);BRD4 has a negative correlation with E-Cadherin(Kendall’s tau-b=﹣0.264,P=0.004))And Vimentin has a positive correlation(Kendall’s tau-b=0.308,P=0.001);Twist has a positive correlation with Vimentin(Kendall’s tau-b=0.279,P=0.002)and has no correlation with E-Cadherin(Kendall’s tau-b=﹣0.139,P=0.132);Vimentin and E-Cadherin have a negative correlation(Kendall’s tau-b=﹣0.359,P<0.001).(2)BRD4 protein expression is correlated with the size of primary tumor(≤2cm,>2 and ≤5cm,>5cm respectively 34.6%,59.3%,83.3%,P=0.012);it is related to molecular classification(Luminal A,Luminal B type,Her-2overexpression type,and triple-negative type were 25%,40.7%,86.7%,92.9%,respectively,P<0.001);related to the time of distant metastasis(≤3 years,4-5years),> 5 years were 68.1%,48.3%,28.6%,P=0.004).It has nothing to do with age,histological grade,vascular tumor thrombus,lymph node metastasis status,number of metastases and metastasis location(P>0.05).(3)Twist protein expression is related to the number of lymph node metastases(63.9%,69.4%,45.5%,84.0% without metastasis,1-3,4-9,and ≥10,respectively,P=0.045).It has nothing to do with age,histological grade,vascular tumor thrombus,primary tumor size,lymph node metastasis status,molecular classification,metastasis location and postoperative distant metastasis time(P>0.05).(4)E-Cadherin protein expression is related to molecular typing(Luminal A,Luminal B,Her-2 overexpression,and triple-negative types were 75.0%,42.4%,36.7%,and 21.4%,respectively,P=0.020);It has nothing to do with age,histological grade,vascular tumor thrombus,primary tumor size,lymph node metastasis status,number,metastasis location and postoperative distant metastasis time(P>0.05).(5)Vimentin protein expression is related to molecular typing(43.8%,42.4%,60.0%,85.7% for Luminal A,Luminal B,Her-2 overexpression,and triple-negative,respectively,P=0.021);and The time of distant metastasis after operation was related(59.4%,31.0%,and 57.1% for ≤3 years,4-5 years,and >5years,respectively,P=0.033).It has nothing to do with age,histological grade,vascular tumor thrombus,primary tumor size,lymph node metastasis status and number,and metastasis location(P>0.05).(6)The expression of BRD4 protein in breast cancer metastases(77.3%)was significantly higher than that in primary breast cancer(56.3%,P<0.001),and the expression of the two was significantly different(Kappa=0.368);Twist protein was in primary breast cancer The expression in foci(66.4%)and the expression in metastases(75.6%)were higher,but the difference was not statistically significant(P=0.126,Kappa=0.131).The expression of E-Cadherin protein in breast cancer metastases(24.4%)was significantly lower than that of the primary tumor(42.9%,P=0.001),and the expression of the two was significantly different(Kappa=0.238);Vimentin protein was in breast cancer metastases The expression of Kappa(73.1%)was significantly higher than that of the primary lesion(52.1%,P<0.001),and the expression of the two was obviously inconsistent(Kappa=0.297).Conclusion:(1)BRD4 participates in the epithelial-mesenchymal transition signaling pathway and promotes epithelial-mesenchymal transition in metastatic breast cancer.(2)In metastatic breast cancer,the degree of epithelial-mesenchymal transition may be related to molecular typing.(3)In metastatic breast cancer,the degree of epithelial-mesenchymal transition of the metastatic lesion is significantly higher than that of the primary lesion.