Methylation of Immune Gene Promoters in Oral and Oropharyngeal Cancer

Int J Mol Sci. 2023 Apr 22;24(9):7698. doi: 10.3390/ijms24097698.

Abstract

The proportion of oral and oropharyngeal squamous cell carcinoma (OOSCC) that can be attributed to human papillomavirus (HPV) infection is growing nowadays. A potential factor indicating the occurrence of HPV-positive OSCC is a change in the degree of methylation of gene promoters that play a key role in the immune response. In this study, we investigated the difference in the methylation of EDARADD, GBP4, HAVCR2, HLA DPB1, IL12RB1, MARCO, and SIGLEC12 gene promoters in samples of healthy oral mucosa versus samples of oral and oropharyngeal cancer. The presence of HPV infection in samples was examined earlier. To determine the difference in methylation of those gene promotors, isolated and bisulfite-modified DNA was analysed by the methylation-specific PCR method. The investigated gene promoters were found to be more hypomethylated in the oral and oropharyngeal cancer samples in comparison to normal tissue. The proportion of unmethylated gene promoters was similar in HPV-positive and HPV-negative cancers, although the data should be confirmed on a larger set of samples. To conclude, in samples of healthy oral mucosa, the investigated gene promoters were found to be methylated in a high percentage (73.3% to 100%), while in oral and oropharyngeal cancer samples, they were methylated in a low percentage (11.1% to 37%), regardless of HPV infection.

Keywords: DNA methylation; HPV; immune system genes; oral and oropharyngeal cancer.

MeSH terms

  • Carcinoma, Squamous Cell* / pathology
  • DNA Methylation
  • Head and Neck Neoplasms* / genetics
  • Humans
  • Mouth Neoplasms* / genetics
  • Mouth Neoplasms* / pathology
  • Oropharyngeal Neoplasms* / genetics
  • Oropharyngeal Neoplasms* / pathology
  • Papillomaviridae / genetics
  • Papillomavirus Infections* / complications
  • Papillomavirus Infections* / epidemiology
  • Papillomavirus Infections* / genetics
  • Squamous Cell Carcinoma of Head and Neck / genetics