Clinical Significance of C-X-C Motif Chemokine Receptor 4 and Integrin αvβ6 Expression in Breast Cancer

Purpose: C-X-C motif chemokine receptor 4 (CXCR4) and integrin alpha v beta 6 play important roles in the malignant progression of multiple cancers. However, it remains unclear whether the expression of one or both proteins in breast cancer (BC) is of clinical significance. In this study, we investigated the expression of CXCR4 and integrin alpha v beta 6 in BC tissues and their correlation with clinicopathological characteristics, including survival. Methods: CXCR4 and alpha v beta 6 expression in 111 BC tissues was examined by immunocytochemistry. Correlations between the expression of the 2 proteins and patient clinicopathological characteristic were investigated using the Kaplan-Meier method and the Cox proportional hazards model. Results: CXCR4 and alpha v beta 6 were overexpressed in BC tissue compared with normal breast tissue. Overexpression of both molecules was related to lymph node status (p = 0.013 and p= 0.022, respectively). alpha v beta 6 overexpression was also associated with tumor size (p= 0.044). A positive correlation was detected between the expression of CXCR4 and alpha v beta 6 (r= 0.649, p = 0.001), and co-overexpression of both molecules was associated with tumor size (p= 0.018) and lymph node metastasis (p= 0.015). Kaplan-Meier analysis revealed that overexpression of CXCR4, alpha v beta 6, or both molecules was associated with short overall survival (OS; p < 0.001, p < 0.001, and p= 0.009, respectively) and disease-free survival (DFS; p < 0.001, p = 0.005, and p = 0.019, respectively). Multivariate analysis indicated that lymph node metastasis was an independent prognostic factor for unfavorable OS and DFS (p = 0.002 and p = 0.005, respectively), whereas co-overexpression of CXCR4 and alpha v beta 6 was an independent prognostic factor only for OS (p = 0.043). Conclusion: CXCR4 and alpha v beta 6 may play synergistic roles in the progression of BC, and co-targeting of CXCR4 and alpha v beta 6 could be a potential strategy for the prevention and treatment of BC.