DNA methylation derived systemic inflammation indices are associated with head and neck cancer development and survival

Oral Oncol. 2018 Oct;85:87-94. doi: 10.1016/j.oraloncology.2018.08.021. Epub 2018 Sep 5.

Abstract

Objectives: Head and neck squamous cell carcinoma (HNSCC) is often associated with chronic systemic inflammation (SI). In the present study, we assessed if DNA methylation-derived SI (mdSI) indices: Neutrophil-to-Lymphocyte ratio (mdNLR) and Lymphocyte-to-Monocyte ratio (mdLMR) are associated with the presence of HNSCC and overall survival (OS).

Materials and methods: We used two peripheral blood DNA methylation datasets: an HNSCC case-control dataset (n = 183) and an HNSCC survival dataset (n = 407) to estimate mdSI indices. We then performed multivariate regressions to test the association between mdSI indices, HNSCC development and OS.

Results: Multivariate logistic regression revealed that elevated mdNLR was associated with increased odds of being an HNSCC case (OR = 3.25, 95% CI = 2.14-5.34, P = 4 × 10-7) while the converse was observed for mdLMR (OR = 0.88, 95% CI = 0.81-0.90, P = 2 × 10-3). In the HNSCC survival dataset, HPV16-E6 seropositive HNSCC cases had an elevated mdLMR (P = 9 × 10-5) and a lower mdNLR (P = 0.003) compared to seronegative patients. Multivariate Cox regression in the HNSCC survival dataset revealed that lower mdLMR (HR = 1.96, 95% CI = 1.30-2.95, P = 0.0013) but not lower mdNLR (HR = 0.68, 95% CI = 0.46-1.00, P = 0.0501) was associated with increased risk of death.

Conclusion: Our results indicate that mdSI estimated by DNA methylation data is associated with the presence of HNSCC and overall survival. The mdSI indices may be used as a valuable research tool to reliably estimate SI in the absence of cell-based estimates. Rigorous validation of our findings in large prospective studies is warranted in the future.

Keywords: DNA methylation; Head and neck cancer; Lymphocyte-to-monocyte ratio; Neutrophil-to-lymphocyte ratio; Overall survival; Systemic inflammation; mdNLR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alcohol Drinking / epidemiology
  • Antibodies, Viral / blood
  • Biomarkers, Tumor
  • C-Reactive Protein / analysis
  • Case-Control Studies
  • Comorbidity
  • CpG Islands
  • DNA Methylation*
  • Datasets as Topic / statistics & numerical data
  • Female
  • Head and Neck Neoplasms / blood
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / virology
  • Human papillomavirus 16 / immunology
  • Human papillomavirus 16 / isolation & purification
  • Humans
  • Inflammation / genetics*
  • Kaplan-Meier Estimate
  • Leukocyte Count
  • Male
  • Middle Aged
  • Odds Ratio
  • Oncogene Proteins, Viral / immunology
  • Papillomavirus Infections / blood
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / mortality
  • Proportional Hazards Models
  • Repressor Proteins / immunology
  • Smoking / epidemiology
  • Squamous Cell Carcinoma of Head and Neck / blood
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • Squamous Cell Carcinoma of Head and Neck / virology

Substances

  • Antibodies, Viral
  • Biomarkers, Tumor
  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Repressor Proteins
  • C-Reactive Protein