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

Abstract

Background: Dickkopf-1 is an inhibitor of the Wnt/β-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/β-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/β-catenin pathway and oral submucous fibrosis pathogenesis.

Keywords: dickkopf-1; methylation; oral squamous cell carcinoma; oral submucous fibrosis.