Elevated levels of Dickkopf-1 are associated with β-catenin accumulation and poor prognosis in patients with chondrosarcoma

PLoS One. 2014 Aug 21;9(8):e105414. doi: 10.1371/journal.pone.0105414. eCollection 2014.

Abstract

Background: Dickkopf-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.

Methods: The 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.

Results: Both 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.

Conclusions: Elevated 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / mortality
  • Bone Neoplasms / pathology
  • Chondrosarcoma / genetics
  • Chondrosarcoma / metabolism*
  • Chondrosarcoma / mortality
  • Chondrosarcoma / pathology
  • Female
  • Gene Expression
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Wnt Signaling Pathway
  • Young Adult
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • beta Catenin

Grants and funding

This work was supported by grants from the National Natural Sciences Foundation of China (81102037). http://www.nsfc.gov.cn. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.