Oncol Lett. 3(2):273-280. 2012. 

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 NLefeuvre MGunduz MGunduz EBeder LBGrenman RFujii MTamamura RTsujigiwa HNagatsuka H.


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.





これまでに、HNSCCの発生と進展に関わる重要な癌関連遺伝子としてDKK3を同定したが(Katase N et al. Oncol Res. 2008)、



(1) HNSCC由来細胞株と組織でのDKK3タンパク発現





(2) HNSCCでのDKK3タンパク発現の臨床的意義

DKK3発現群はdisease free survivalが有意に短かった。

また、overall survivalも短い傾向を示した。





Oncogenic functionを有する可能性」が示唆された。