Expression and methylation of Dickkopf-1 in the pathogenesis and malignant transformation of oral submucous fibrosis.

BACKGROUND: Dickkopf-1 is an inhibitor of the Wnt/beta-catenin pathway, but the role of Dickkopf-1 in oral submucous fibrosis remains unclear. We evaluated the protein expression and gene methylation levels of dickkopf-1 to determine the mechanism underlying abnormal Wnt/beta-catenin pathway activation. METHODS: Healthy mucosa, oral submucous fibrosis, oral squamous cell carcinoma, and cancer-adjacent tissues were collected. The expression and promoter methylation levels of dickkopf-1 were analyzed. RESULTS: The expression levels of dickkopf-1 in oral submucous fibrosis and oral squamous cell carcinoma tissues were lower than those in healthy and cancer-adjacent tissues. The methylation levels of the dickkopf-1 gene in oral submucous fibrosis and oral squamous cell carcinoma tissues were higher than those in healthy and cancer-adjacent tissues. Dickkopf-1 expression was negatively correlated with dickkopf-1 gene methylation. CONCLUSIONS: High dickkopf-1 methylation levels in oral submucous fibrosis and oral squamous cell carcinoma tissues may decrease dickkopf-1 expression, which may induce an abnormal activation of the Wnt/beta-catenin pathway and oral submucous fibrosis pathogenesis.