ZNF582 hypermethylation as a prognostic biomarker for malignant transformation of oral lesions

Oral Dis. 2023 Mar;29(2):505-514. doi: 10.1111/odi.13946. Epub 2021 Jul 1.

Abstract

Objectives: This hospital-based cohort study evaluated whether ZNF582 and PAX1 methylation levels at baseline can be used as biomarkers to identify lesions with a high potential for malignant transformation in patients with normal mucosa and oral potentially malignant disorders.

Patients and methods: We recruited 171 adult patients with normal mucosa and oral potentially malignant disorders in 2012-2014. They were followed until 2017. Outcomes, including advanced histopathological findings and oral cancer occurrence, were obtained from medical charts, the Taiwan Cancer Registry, and cause-of-death data. Kaplan-Meier analysis and Cox proportional hazards regression models were used to examine the association of ZNF582 and PAX1 methylation levels at baseline with subsequent outcome occurrences.

Results: After 260,192 days of follow-up, 11 cases of oral cancer and 4 cases of advanced histopathological progression occurred. Patients with higher ZNF582 and PAX1 methylation levels at baseline had a higher incidence of disease progression. After adjustment for all studied factors using Cox proportional hazards regression models, ZNF582m level (adjusted hazard ratio, 11.41; 95% CI, 2.05-63.36; p = 0.005) was the only significant and independent predictor of disease progression.

Conclusions: ZNF582 hypermethylation can be an effective and noninvasive biomarker for identifying oral lesions with a high potential for malignant transformation.

Keywords: ZNF582; biomarker; hypermethylation; malignant transformation; oral potentially malignant disorders; oral squamous cell carcinoma.

MeSH terms

  • Adult
  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Cohort Studies
  • DNA Methylation
  • Disease Progression
  • Humans
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Mouth Neoplasms* / genetics
  • Mouth Neoplasms* / pathology
  • Paired Box Transcription Factors / genetics
  • Paired Box Transcription Factors / metabolism
  • Prognosis

Substances

  • Biomarkers, Tumor
  • Paired Box Transcription Factors
  • Kruppel-Like Transcription Factors
  • ZNF582 protein, human