BACKGROUND: Dickkopf-3 (DKK3) may act as a tumor suppressor as it is down-regulated in various types of cancer. This study assessed the DKK3 protein expression in gastric cancer and its potential value as a prognostic marker. METHODS: DKK3 expression was evaluated by immunohistochemistry in 158 gastric cancer samples from patients who underwent gastrectomy from 2002 to 2008. Clinicopathological parameters and survival data were analyzed. RESULTS: Loss of DKK3 expression was found in 64 of 158 (40.5%) samples, and it was associated with advanced T stage (p < 0.001), lymph node metastasis (p < 0.001), UICC TNM stage (p < 0.001), tumor location (p = 0.029), lymphovascular invasion (p = 0.035), and perineural invasion (p = 0.032). Patients without DKK3 expression in tumor cells had a significantly worse disease-free and overall survival than those with DKK3 expression (p < 0.001, and p = 0.001, respectively). TNM stage (p = 0.028 and p < 0.001, respectively) and residual tumor (p < 0.001 and p = 0.003, respectively) were independent predictors of disease-free and overall survival. Based on the preoperative clinical stage assessed by computed tomography (CT), loss of DKK3 expression was predominantly associated with worse prognosis in patients with clinically node-negative advanced gastric cancer (AGC). The combination of DKK3 expression status and CT increased the accuracy of CT staging for predicting lymph node involvement from 71.5 to 80.0% in AGC patients. CONCLUSION: Loss of DKK3 protein expression was significantly associated with poor survival in patients with gastric cancer and was strongly correlated with the TNM stage. DKK3 might be a potential biomarker of lymph node involvement that can improve the predictive power of CT.
BACKGROUND:Dickkopf-3 (DKK3) may act as a tumor suppressor as it is down-regulated in various types of cancer. This study assessed the DKK3 protein expression in gastric cancer and its potential value as a prognostic marker. METHODS:DKK3 expression was evaluated by immunohistochemistry in 158 gastric cancer samples from patients who underwent gastrectomy from 2002 to 2008. Clinicopathological parameters and survival data were analyzed. RESULTS: Loss of DKK3 expression was found in 64 of 158 (40.5%) samples, and it was associated with advanced T stage (p < 0.001), lymph node metastasis (p < 0.001), UICC TNM stage (p < 0.001), tumor location (p = 0.029), lymphovascular invasion (p = 0.035), and perineural invasion (p = 0.032). Patients without DKK3 expression in tumor cells had a significantly worse disease-free and overall survival than those with DKK3 expression (p < 0.001, and p = 0.001, respectively). TNM stage (p = 0.028 and p < 0.001, respectively) and residual tumor (p < 0.001 and p = 0.003, respectively) were independent predictors of disease-free and overall survival. Based on the preoperative clinical stage assessed by computed tomography (CT), loss of DKK3 expression was predominantly associated with worse prognosis in patients with clinically node-negative advanced gastric cancer (AGC). The combination of DKK3 expression status and CT increased the accuracy of CT staging for predicting lymph node involvement from 71.5 to 80.0% in AGC patients. CONCLUSION: Loss of DKK3 protein expression was significantly associated with poor survival in patients with gastric cancer and was strongly correlated with the TNM stage. DKK3 might be a potential biomarker of lymph node involvement that can improve the predictive power of CT.
Authors: T Tsuji; I Nozaki; M Miyazaki; M Sakaguchi; H Pu; Y Hamazaki; O Iijima; M Namba Journal: Biochem Biophys Res Commun Date: 2001-11-23 Impact factor: 3.575