DNA methylation derived systemic inflammation indices are associated with head and neck cancer development and survival. (October 2018) - Ambatipudi, Srikant
Highlights: DNA methylation data was used to derive systemic inflammation indices. Elevated mdNLR and lower mdLMR were associated with the risk of HNSCC. HPV16-E6 seropositive HNSCCs had an elevated mdLMR and a lower mdNLR. Lower mdLMR was associated with increased risk of death. 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.