Abstract 1701: Clinical significance of serum and tissue Dickkopf-1 in patients with gastric cancer

Abstract Background: Dickkopf-1 (DKK-1) is a secreted protein known as a negative regulator of the Wnt signaling pathway and involved in embryonic development and tumorigenesis. Clinical significance of serum DKK-1 and tissue DKK-1 expression in gastric cancer has not been clarified. Methods: Serum concentrations of DKK-1 were assessed by enzyme-linked immunosorbent assay in 153 gastric cancer patients and 33 healthy controls. We also obtained serum CEA (ng/mL) and CA19-9 (U/mL) values by chemiluminescence immunoassay. For tissue DKK-1, we performed immunohistochemical staining for DKK-1 in 144 cancer specimens of 153 patients and in additional 265 consecutive gastric cancer specimens. Results: Serum DKK-1 concentrations were significantly higher in gastric cancer patients (56.27 pg/mL) than in healthy controls (30.50 pg/mL, p=0.018). With 36.3150 pg/mL of cut-off value, sensitivity and specificity for gastric cancer diagnosis were 80.4% and 78.8%, respectively. Gastric cancer patients with a serum DKK-1 of 60.0 pg/mL or higher had a significantly diminished survival compared with patients whose serum DKK-1 were lower (p=0.033). By immunohistochemistry, DKK-1 overexpression in cancer specimens was significantly correlated with increased serum DKK-1 concentrations (correlation coefficient, 0.395; p<0.001). The cancer patients with DKK-1 overexpression had a significantly worse prognosis than the patients without DKK-1 expression in this cohort (p=0.004) and additional consecutive cases (p=0.030). By multivariate Cox regression model, DKK-1 expression status predicted patient prognosis independently of pTNM stage and histologic differentiation in consecutive cases (p=0.018). Conclusion: Increased serum DKK-1 concentrations and overexpression of DKK-1 in gastric cancer tissue may contribute to diagnosing gastric cancer and predicting cancer patient outcome. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1701. doi:1538-7445.AM2012-1701