Abstract
BackgroundDickkopf-1 (DKK1) is an antagonist of Wnt/β-catenin signaling implicated in tumorigenesis. However, the biological role of DKK1 and β-catenin involved in chondrosarcoma has not been sufficiently investigated. This study was designed to investigate the expression profiles of DKK1 and β-catenin, and to clarify their clinical values in chondrosarcoma.MethodsThe mRNA and protein levels of DKK1 and β-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 β-catenin were investigated by immunohistochemistry. The associations among DKK1 level, β-catenin accumulation, clinicopathological factors and the overall survival were separately evaluated.ResultsBoth DKK1 and β-catenin levels were remarkably elevated in chondrosarcoma compared with the corresponding non-tumor tissues. High DKK1 level and positive β-catenin accumulation in chondrosarcoma specimens were 58.7% and 53.9%, respectively. Elevated DKK1 level significantly correlated with positive β-catenin accumulation, and they were remarkably associated with histological grade and Musculoskeletal Tumor Society stage. Furthermore, DKK1 level and β-catenin accumulation had significant impacts on the prognosis of chondrosarcoma patients. Multivariate analysis revealed that DKK1 level was an independent prognostic factor for overall survival.ConclusionsElevated DKK1 levels associated with β-catenin accumulation play a crucial role in chondrosarcoma. DKK1 can serve as a novel predictor of poor prognosis in patients with chondrosarcoma.
Highlights
Chondrosarcoma is a malignant cartilage-forming tumor, accounting for approximately 20% of bone malignancies and presenting with a wide spectrum of clinical behaviors [1]
Our findings suggest that elevated levels of DKK1 and b-catenin play a role in the pathogenesis of chondrosarcoma, and DKK1 can be recognized as an independent factor to predict the prognosis of chondrosarcoma patients
To identify whether the expression levels of DKK1 and bcatenin are involved in the pathogenesis of chondrosarcoma, we measured the mRNA and protein levels of DKK1 and b-catenin in chondrosarcomas and the corresponding non-tumor tissues
Summary
Chondrosarcoma is a malignant cartilage-forming tumor, accounting for approximately 20% of bone malignancies and presenting with a wide spectrum of clinical behaviors [1]. The Dickkopf (DKK) genes were Wnt antagonists originally identified as inducers of head formation in Xenopus and comprised an evolutionary conserved gene family of four members (DKK1-4) and a unique DKK3-related gene, soggy [9,10]. DKK1 was identified as a downstream target of the b-catenin/ TCF pathway and participates in a negative feedback loop in the Wnt signaling pathway [12]. These finding suggest that DKK1 associated with b-catenin accumulation plays an important role in cancerogenesis [13]. Dickkopf-1 (DKK1) is an antagonist of Wnt/b-catenin signaling implicated in tumorigenesis. This study was designed to investigate the expression profiles of DKK1 and b-catenin, and to clarify their clinical values in chondrosarcoma
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