Serum Dickkopf-1 expression level positively correlates with a poor prognosis in breast cancer

Background: The different expression level of Dickkopf-1 (DKK-1) in different cancers shows that the function of DKK-1 depends on the histological type of the cancer cells and the tissue microenvironment. To our knowledge, the serum expression level of DKK-1 in breast cancer is little known. Methods: Blood samples from 125 consecutive patients diagnosed with breast cancer and 53 control subjects from March 2008 to August 2013 were investigated. Serum DKK-1 expression levels were measured by enzyme-linked immunosorbent assay (ELISA). The overall survival (OS) and relapse-free survival (RFS) analyzed by log-rank test, and survival curves were plotted according to Kaplan-Meier. Results: The mean serum level of DKK-1 in patients with breast cancer was 4.99 +/- 1.50 ng/mL, and was significantly higher than that in healthy individuals (1.88 +/- 0.81 ng/mL, P < 0.001). DKK-1 level correlated significantly with TNM stage (P = 0.009), tumor grade (P = 0.02), lymph node metastasis (P = 0.001), and expression of HER2 (P = 0.002). The DKK-1 expression level was classified as high or low in relation to the median value, and patients with breast cancer (n = 125) were divided into a high expression group (n = 63) and a low expression group (n = 62). The Kaplan-Meier method for survival analysis showed that the patients with a high serum DKK-1 level had a poorer OS (48.7% vs. 81.3%, p = 0.01) and RFS (24.3% vs. 71.6%, p = 0.003) than those with a low expression level. The multivariate Cox regression analysis indicated that serum DKK-1 level was independent prognostic factors for OS and RFS. Conclusions: Serum DKK-1 level can be used as a noninvasive biomarker for the prognosis of breast cancer.