Elevated Levels of Dickkopf-1 Are Associated with β-Catenin Accumulation and Poor Prognosis in Patients with Chondrosarcoma

Background: Dickkopf-1 (DKK1) is an antagonist of Wnt/beta-catenin signaling implicated in tumorigenesis. However, the biological role of DKK1 and beta-catenin involved in chondrosarcoma has not been sufficiently investigated. This study was designed to investigate the expression profiles of DKK1 and beta-catenin, and to clarify their clinical values in chondrosarcoma. Methods: The mRNA and protein levels of DKK1 and beta-catenin in fresh chondrosarcoma and the corresponding non-tumor tissues were analyzed by Real-time PCR and Western blot, respectively. The protein expression patterns of DKK1 and bcatenin were investigated by immunohistochemistry. The associations among DKK1 level, beta-catenin accumulation, clinicopathological factors and the overall survival were separately evaluated. Results: Both DKK1 and beta-catenin levels were remarkably elevated in chondrosarcoma compared with the corresponding non-tumor tissues. High DKK1 level and positive beta-catenin accumulation in chondrosarcoma specimens were 58.7% and 53.9%, respectively. Elevated DKK1 level significantly correlated with positive beta-catenin accumulation, and they were remarkably associated with histological grade and Musculoskeletal Tumor Society stage. Furthermore, DKK1 level and bcatenin accumulation had significant impacts on the prognosis of chondrosarcoma patients. Multivariate analysis revealed that DKK1 level was an independent prognostic factor for overall survival. Conclusions: Elevated DKK1 levels associated with beta-catenin accumulation play a crucial role in chondrosarcoma. DKK1 can serve as a novel predictor of poor prognosis in patients with chondrosarcoma.