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

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.

SUBMITTER: Ambatipudi S 

PROVIDER: S-EPMC6156796 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature