Diagnostic and prognostic potential of serum angiopoietin-2 expression in human breast cancer

Abstract

Background: Accumulating evidence demonstrated a link of increased expression of Angiopoietin-2 (Ang-2) with invasive and metastatic phenotypes of various types of human cancers. However, until now, the serum level and its diagnostic and prognostic potential in breast cancer have not been investigated.

Methods: Enzyme-linked immunosorbent assays were used to measure the levels of Ang-2. Sensitivity, specificity and area under curve (AUC) for serum Ang-2 levels were determined using receiver operator characteristic (ROC) analysis. Survival curves were plotted using the Kaplan-Meier method and differences in survival rates were analyzed using the log-rank test. Prognostic relevance of each variable to overall survival (OS) and disease-free survival (DFS) were analyzed using the Cox regression model.

Results: Serum expression of Ang-2 in patients with breast cancer was significantly higher than healthy control group (3171 ± 1024 vs. 1800 ± 874 pg/ml, P < 0.0001). ROC curve analysis showed that at the optimal cut-off (2558.5 pg/ml), serum level of Ang-2 had a sensitivity of 78.3% and a specificity of 77.0% for distinguishing breast cancer patients from healthy controls with an area under the curve (AUC) of 0.836 (P < 0.001, 95% confidence interval: 0.787-0.885). The 5-year OS of high Ang-2 expression group was significantly shorter than that of low Ang-2 expression group (55.9% vs. 80.3%; P = 0.018). Moreover, the 5-year DFS of high Ang-2 expression group was also significantly shorter than that of low Ang-2 expression group (46.0% vs. 68.7%; P = 0.029).

Conclusions: Our data indicate that serum Ang-2 level has potential value for early detection of breast cancer. Furthermore, Ang-2 has prognostic value in patients with breast cancer.

Keywords: Angiopoietin-2; breast cancer; diagnosis; prognosis.

Figure 1

Serum Ang-2 expression level in 143 patients with breast cancer and 100 healthy controls. Serum expression level of Ang-2 in patients with breast cancer was significantly higher than healthy control group (3171 ± 1024 vs. 1800 ± 874 pg/ml, P < 0.0001).

Figure 2

Receiver operator characteristic (ROC) analysis showed that at the optimal cut-off (2558.5 pg/ml), serum level of Ang-2 had a sensitivity of 78.3% and a specificity of 77.0% for distinguishing breast cancer patients from healthy controls with an area under the curve (AUC) of 0.836 (P < 0.001, 95% confidence interval: 0.787-0.885).

Figure 3

Kaplan-Meier curves of patients with breast cancer. Elevated Ang-2 level was associated with shorter overall survival (A) and disease-free survival (B).