Objective  To investigate the relationship between Dickkopf -1 (DKK-1) gene methylation status in oral squamous cell carcinoma (OSCC), oral swabs and disease progression as well as its clinical significance.

  Methods  A total of 67 OSCC patients were selected as OSCC group, whose ipsilateral and contralateral OS specimens and surgical tissue specimens were collected. The healthy oral mucosa of 30 patients with impacted wisdom teeth and 30 patients with oral submucosal fibrosis (OSF) were selected as control group and pre-cancerous group. Immunohistochemical staining method was used to detect DKK-1 protein expression, while the bisulphite-converting method and quantitative methylation-specific polymerase chain reaction (qMSP) were used to detect the methylation level of DKK-1 gene.

  Results  The positive expression rates of DKK-1 protein in the pre-cancerous group (66.67%, 20/30) and OSCC group (20.90%, 14/67) were significantly lower than that in control group (93.33%, 28/30), and the OSCC group was significantly lower than the pre-cancerous group (P < 0.001). The methylation levels of DKK-1 gene in tumor tissues and OS samples of the OSCC group were significantly higher than those in pre-cancerous group and control group (P < 0.001). Spearman correlation coefficient analysis showed that the methylation level of DKK-1 gene in the ipsilateral OS speciments was positively correlated with that of DKK-1 in the tissues (r_s=0.672, P < 0.001). The area under the curve (AUC) of DKK-1 gene methylation level in tissue and ipsilateral OS specimens for differential diagnosis of OSCC and precancerous lesions was 0.799 (95%CI, 0.713 to 0.884) and 0.843 (95%CI, 0.762 to 0.924), respectively. The methylation of DKK-1 in OS samples was more pronounced in early stage (Z=2.354, P=0.021) and in patients with well-differentiated tumors (Z=3.731, P < 0.001).

  Conclusion  Hypermethylation of DKK-1 gene in OS specimens collected from the lesion sites can be used for monitoring OSF carcinogenesis and early diagnosis of OSCC.