Purpose: C-X-C motif chemokine receptor 4 (CXCR4) and integrin αvβ6 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 αvβ6 in BC tissues and their correlation with clinicopathological characteristics, including survival. Methods: CXCR4 and αvβ6 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 αvβ6 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). αvβ6 overexpression was also associated with tumor size (p = 0.044). A positive correlation was detected between the expression of CXCR4 and αvβ6 (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, αvβ6, 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 αvβ6 was an independent prognostic factor only for OS (p = 0.043). Conclusion CXCR4 and αvβ6 may play synergistic roles in the progression of BC, and co-targeting of CXCR4 and αvβ6 could be a potential strategy for the prevention and treatment of BC.

PURPOSE: Vesicle-associated membrane protein 8 (VAMP8) is a soluble N-ethylmaleimide-sensitive factor receptor protein that participates in autophagy by directly regulating autophagosome membrane fusion and has been reported to be involved in tumor progression. Nevertheless, the expression and prognostic value of VAMP8 in breast cancer (BC) remain unknown. This study aimed to evaluate the clinical significance and biological function of VAMP8 in BC. METHODS: A total of 112 BC samples and 30 normal mammary gland samples were collected. The expression of VAMP8 was assessed in both BC tissues and normal mammary gland tissues via a two-step immunohistochemical detection method. RESULTS: The expression of VAMP8 in BC tissues was significantly higher than that in normal breast tissues. Furthermore, increased VAMP8 expression was significantly correlated with tumor size (p=0.007), lymph node metastasis (p=0.024) and recurrence (p=0.001). Patients with high VAMP8 expression had significantly lower cumulative recurrence-free survival and overall survival (p < 0.001 for both) than patients with low VAMP8 expression. In multivariate logistic regression and Cox regression analyses, lymph node metastasis and VAMP8 expression were independent prognostic factors for BC. CONCLUSION: VAMP8 is significantly upregulated in human BC tissues and can thus be a practical and potentially effective surrogate marker for survival in BC patients.
Autophagy ; Biomarkers ; Breast Neoplasms* ; Breast* ; Humans ; Logistic Models ; Lymph Nodes ; Mammary Glands, Human ; Membrane Fusion ; Methods ; N-Ethylmaleimide-Sensitive Proteins ; Neoplasm Metastasis ; Prognosis ; R-SNARE Proteins* ; Recurrence