Over the past few years, an increasing number of studies have focused on exploring the risk factors of breast cancer in order to prevent it. Up to now, many molecular markers have been used for prognosis of breast cancer patients, including Ki-67, Bcl-2, HER-2, ER, PR, P53, PAR1, and FGFR1 [
17]-[
21]. These markers are all correlated with patient outcomes. However, the biological potential of breast cancer is difficult to predict completely with the use of current standard risk factors. Therefore, more persuasive prognostic indicators should be explored for the comprehensive evaluation of breast cancer patients.
DKK-1, DKK-2, DKK-3, and DKK-4, together with a special DKK-3 related protein termed Soggy (Sgy), compose a family of DKK-related genes. DKK-1, DKK-2, DKK-3, and DKK-4 contain 2 discrete cysteine-rich domains, in which the positions of 10 cysteine residues are supremely conserved among family members. DKK-1 and DKK-4, but not DKK-2, DKK-3 or Sgy, have been shown to suppress the Wnt-induced secondary axis induction in Xenopus embryos [
22],[
23]. DKK-4 was found to show high specificity for gastric cancer [
24]. DKK-1, which was involved in some aspects of embryonic development, was detected in mature human tissues, mainly in the placenta. Specifically, Wnt-1 protein binds to the frizzled receptor and the low-density lipoprotein receptor-related protein-5/6, triggering signals important for proliferation via β-catenin. DKK-1 binds to low-density lipoprotein receptor-related protein-5/6 and blocks interaction with Wnt-1 resulting in β-catenin degradation and effects on proliferation [
25]. Other result showed that DKK-1 functioned not only as an antagonist of the Wnt/β-catenin pathway but also as an agent that could up-regulate other Wnt signaling pathways if the requisite Wnt/receptor combinations were available. DKK-1 also can suppress cell growth and induces apoptotic cell death by activating the c-Jun N-terminal kinase pathway [
26]. The expression and roles of DKK-1 are different in various cancers, current studies have reported that overexpression of DKK-1 is found in many malignant tumors, including lung cancer, esophageal carcinomas, cervical cancer, and HCC, indicating a potential oncogenic function of DKK-1 [
10]-[
13]. However, paradoxically, the expression of DKK-1 was down-regulated significantly in human colon cancer, gastric cancer and melanoma [
14]-[
16]. Therefore, the different function of DKK-1 in different cancer types depends on the histological type of the cancer cells and the tissue microenvironment. However, to our knowledge the expression of DKK-1 in breast cancer is little known. In the present study we investigated the expression of DKK-1 in patients’ serum to establish if DKK-1 can be used as a novel prognostic biomarker in human breast cancer. In this study, we had three findings. Firstly, the serum levels of DKK-1 in patients with breast cancer was significantly higher than that in healthy individuals, and high serum levels of DKK-1 was found to significantly correlate with TNM stage, tumor grade, lymph node metastasis, and expression of HER2. Secondly, Kaplan–Meier analysis showed that breast cancer patients with high serum DKK-1 expression level had distinctly shorter overall survival and relapse-free survival. Thirdly, univariate and multivariate analyses showed that the serum DKK-1 level was independent prognostic parameter of overall survival and relapse-free survival in breast cancer patients. All the results suggested that serum DKK-1 level was befitting to predict prognosis of breast cancer patients after surgery.