Abstract
BACKGROUND: Dickkopf-1 (DKK1) is a Wnt/ß-catenin pathway antagonist related to gastric cancer (GC) carcinogenesis. However, the prognostic role of combined DKK1 and ß-catenin expression in advanced GC (AGC) is not clear. METHODS: In total, 158 patients with AGC who underwent gastric resection were enrolled in this study. DKK1 and ß-catenin expression was evaluated in whole tumor sections by immunohistochemistry. RESULTS: DKK1 expression was high in 73 (46.2%) patients, while ß-catenin expression was positive in 51 (32.3%) patients. The expression of DKK1 was positively correlated with that of ß-catenin (P < 0.001). The combined expression of DKK1 and ß-catenin was significantly associated with high N stage (N2 and N3) (P = 0.042). In addition, patients with high DKK expression demonstrated poorer overall (OS) (P < 0.001) and disease-free survival (DFS) (P = 0.001). However, there were no differences between high DKK1 expression with ß-catenin positivity and high DKK1 expression with ß-catenin negativity (OS, P = 0.379: DFS, P = 0.255). Multivariate analysis revealed that high DKK1 alone or high DKK1 with ß-catenin positivity were independent prognostic factors for both OS (high DKK1: hazard ratio [HR], 2.130; 95% confidence interval [CI]; 1.370-3.312, P = 0.001; high DKK1 with ß-catenin positivity: HR, 2.140; 95% CI, 1.343-3.409: P = 0.001) and DFS (high DKK1: HR, 2.092; 95% CI, 1.180-3.708; P = 0.012; high DKK1 with ß-catenin positivity: HR, 2.357; 95% CI, 1.291-4.306; P = 0.005). CONCLUSION: Our results indicate that high DKK1 expression regardless of ß-catenin positivity is a crucial prognostic factor for predicting tumor recurrence and survival in patients with resected AGC.