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.

Comparison of Immunohistochemical Markers in Oral Submucous Fibrosis and Oral Submucous Fibrosis Transformed to Oral Squamous Cell Carcinoma—A Systematic Review and Meta-Analysis

“…of positive cells/No. of cells) × 100 [29], and H-score is calculated as 1 × (% of 1 + cells) + 2 × (% of 2 + cells) + 3 × (% of 3 + cells) [30].…”

“…Further comprehensive evaluation against the inclusion criteria excluded 32 articles. The total of 14 articles were included in the systematic review [20][21][22][23][24][25][26][27]29,30,[33][34][35][36], as shown in Figure 1.…”

“…The following biomarkers were studied: survivin [20], hTERT [21], β1 integrin [22], caspase-3 [23], α-SMA [25,29], COX-2 [24], p53 [24,27], MDM2 [24], PTEN [25], CTGF [26], Ki-67 [29,36], CD105 [29], OCT-3 [33], Dickkopf-1 [30], Lysyl oxidase [34], CD1a [35], CD207 [35], CD303 [35], and p16 [36]. Of the total 14 articles, 9 studies were conducted in Indian [21][22][23][24][25][26]29,34,36], 4 in other Asian [20,27,30,33], and 1 in Brazilian population [35]. The non-transformed group and transformed group were comprised of 795 and 637 patients, respectively.…”

“…A total of 14 studies are included in the systematic review, in which immunoexpression of 19 biomarkers were evaluated [20][21][22][23][24][25][26][27]29,30,[33][34][35][36]. The following biomarkers were studied: survivin [20], hTERT [21], β1 integrin [22], caspase-3 [23], α-SMA [25,29], COX-2 [24], p53 [24,27], MDM2 [24], PTEN [25], CTGF [26], Ki-67 [29,36], CD105 [29], OCT-3 [33], Dickkopf-1 [30], Lysyl oxidase [34], CD1a [35], CD207 [35], CD303 [35], and p16 [36]. Of the total 14 articles, 9 studies were conducted in Indian [21][22][23][24][25][26]29,34,36], 4 in other Asian [20,27,30,…”

“…The non-transformed group and transformed group were comprised of 795 and 637 patients, respectively. Six out of sixteen articles specified the gender of the patients in the non-transformed group, which demonstrated male to female proportion as 227:56 [21,[24][25][26]30,35]. In the transformed group, the male-female proportion of the patients was stated in seven articles [20,21,[24][25][26]30,35], which included 188 males to 31 females.…”