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

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

Srikant Ambatipudi  1 , Ryan Langdon  2 , Rebecca C Richmond  2 , Matthew Suderman  2 , Devin C Koestler  3 , Karl T Kelsey  4 , Nabila Kazmi  2 , Christopher Penfold  5 , Karen M Ho  6 , Wendy McArdle  6 , Susan M Ring  2 , Miranda Pring  5 , Tim Waterboer  7 , Michael Pawlita  7 , Tom R Gaunt  2 , George Davey Smith  2 , Steve Thomas  5 , Andy R Ness  5 , Caroline L Relton  2
Affiliations

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

Srikant Ambatipudi et al. Oral Oncol. 2018 Oct.

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.

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Conflict of interest statement

Conflict of interest

The authors declare that they have no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Methylation derived systemic inflammation indices in the HNSCC case-control and survival datasets. A. mdNLR in pre-treatment HNSCC cases and controls. B. mdLMR in pre-treatment HNSCC cases and controls. C. mdNLR in HNSCC cases who died during follow-up and those who were alive. D. mdLMR in HNSCC cases who died during follow-up and those who were alive.
Fig. 2.
Fig. 2.
Overall survival curve for methylation derived systemic inflammation indices A. mdNLR (above and below median) and B. mdLMR (above and below median).
See this image and copyright information in PMC

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