Absence of Dickkopf (Dkk)-3 protein expression is correlated with longer disease-free survival and lower incidence of metastasis in head and neck squamous cell carcinoma

Katase,Naoki; Lefeuvre,Mathieu; Gunduz,Mehmet; Gunduz,Esra; Beder,Levent   Bekir; Grenman,Reidar; Fujii,Masae; Tamamura,Ryo; Tsujigiwa,Hidetsugu; Nagatsuka,Hitoshi

doi:10.3892/ol.2011.473

Absence of Dickkopf (Dkk)-3 protein expression is correlated with longer disease-free survival and lower incidence of metastasis in head and neck squamous cell carcinoma

Authors:
- Naoki Katase
- Mathieu Lefeuvre
- Mehmet Gunduz
- Esra Gunduz
- Levent Bekir Beder
- Reidar Grenman
- Masae Fujii
- Ryo Tamamura
- Hidetsugu Tsujigiwa
- Hitoshi Nagatsuka
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Affiliations: Department of Oral Pathology and Medicine, Graduate school of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Kita-ku, Okayama, 700-8525 Japan, Department of Medical Genetics, Faculty of Medicine, Fatih University, Ankara, Turkey, Department of Otolaryngology Head and Neck Surgery, Wakayama Medical University, Wakayama, Japan, Department of Otorhinolaryngology and Head and Neck Surgery, Turku University Central Hospital and Department of Medical Biochemistry and Molecular Biology, University of Turku and University Central Hospital, Turku, Finland
Published online on: November 8, 2011 https://doi.org/10.3892/ol.2011.473
Pages: 273-280

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Abstract

Head and neck squamous cell carcinoma (HNSCC) is one of the most frequently occurring types of cancer worldwide. We focused on the fact that the aberrant function of Wnt/β-catenin signaling is a frequent event in malignancies. Dickkopf (Dkk)-3 is a major negative regulator of Wnt/β‑catenin signaling, which is a known tumor suppressor and is down‑regulated in various types of cancer. However, the expression profile of the Dkk-3 protein in HNSCC has not yet been reported. The present study was conducted to investigate Dkk-3 protein expression in 90 cases of HNSCC tissue samples and HNSCC-derived cell lines. In contrast to findings available on other types of cancer, the Western blot analysis revealed that HNSCC cell lines expressed the Dkk-3 protein. In immunohistochemistry, 76 cases (84.4%) out of 90 tissue samples were Dkk-3-positive, whereas only 14 cases (15.6%) were negative. Notably, survival analysis showed that the Dkk-3 (-) group exhibited significantly longer disease-free survival (p=0.038), metastasis-free survival (p=0.013) and longer overall survival (p=0.155). The results showed that the Dkk-3 protein was dominantly expressed and may be involved in carcinogenesis and metastasis in HNSCC. Moreover, the findings suggest that the function of Dkk-3 differs depending on the tissue of origin, and that it may exert an oncogenic function in HNSCC.

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