Promotor hypermethylated genes: Prospective diagnostic biomarkers in oral cancerogenesis

J Craniomaxillofac Surg. 2018 Oct;46(10):1737-1740. doi: 10.1016/j.jcms.2018.07.019. Epub 2018 Jul 29.

Abstract

The advancements in epigenetics of oral squamous cell carcinoma (OSCC), are made in regard to DNA hypermethylation of MGMT, DAPK, ECAD (E-cadherin) and p16, as an important component of oral carcinogenesis and new potential biomarkers in molecular diagnostic strategies. The objective of the study was to evaluate the methylation status of the proposed genes and their possible role in the tumor genesis and diagnosis of OSCC.

Materials and methods: From sixty surgically treated and molecularly analyzed patients, we obtained three groups of bioptical materials: tumor, normal contralateral and healthy tissues. Comparison of the frequencies of DNA methylation for all transcripts was utilized to validated their potential role in the cancerogenesis and detection of OSCC.

Results: The most often methylated genes in the tumor samples were ECAD, MGMT, DAPK followed by p16 genes (90% vs 75% vs 75% vs 52,5%), respectively. We observed frequent methylated genes in contralateral mucosa and consistently unmethylated- 0% in healthy samples. ECAD methylated genes showed the highest sensitivity for diagnosing OSCC in tumor and contralateral tissues (90% and 89,7% respectively, with a specificity of 100%).

Conclusion: ECAD and MGMT have tumor-specific signatures and can be considered as potential noninvasive diagnostic biomarkers in OSCC.

Keywords: Biomarkers; DNA promoter hypermethylated genes; Diagnostic accuracy; OSCC.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Cadherins / genetics
  • Carcinogenesis / genetics*
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / genetics
  • Case-Control Studies
  • DNA Methylation* / genetics
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / genetics
  • DNA, Neoplasm / genetics
  • Death-Associated Protein Kinases / genetics
  • Genes, p16
  • Humans
  • Mouth Neoplasms / diagnosis*
  • Mouth Neoplasms / genetics
  • Promoter Regions, Genetic / genetics*
  • Tumor Suppressor Proteins / genetics

Substances

  • Biomarkers, Tumor
  • Cadherins
  • DNA, Neoplasm
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • Death-Associated Protein Kinases
  • DNA Repair Enzymes