Distribution of PAX1 and ZNF582 Hypermethylation in the Oral Exfoliated Cells of Oral Squamous Cell Carcinoma.

Abstract

Background: The DNA methylation statuses of PAX1 and ZNF582 show great promise as biomarkers for the detection of oral squamous cell carcinoma (OSCC). This study aims to investigate the distribution of PAX1 or ZNF582 methylation in the exfoliated oral epithelial cells (OECs) of OSCC.

Methods: Methylation data from 528 tumors and 50 adjacent nontumor tissues were acquired from The Cancer Genome Atlas and analyzed using UALCAN database. Sixty-one OSCC cases from Peking University School and Hospital of Stomatology were included in this study and the exfoliated OECs collected by oral swabs were collected from the cancerous lesion (CL), adjacent normal (AN), and contralateral normal (CN) sites. The methylation levels of these 2 genes in different sites were evaluated.

Results: PAX1 and ZNF582 were both hypermethylated in OSCC compared with nontumor sites but showed different methylation patterns within the oral environment. Generally, a CL-centric methylation pattern of PAX1 where methylation levels decrease gradually from CL through AN to CN was observed, suggesting a field cancerization effect. ZNF582 methylation levels are significantly higher at lesion sites compared with normal sites, but no significant difference is observed between AN and CN. Coexistence of ZNF582 methylation in CL and AN or CN sites was also observed in some patients with OSCC. Furthermore, ZNF582 methylation was more sensitive among patients with OSCC.

Conclusions: DNA methylation detection of PAX1 and ZNF582 in the exfoliated OECs is helpful for OSCC diagnosis. Hypermethylated PAX1 and ZNF582 show different methylation patterns in the oral cavity of patients with OSCC.