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

被引：16

作者：

Ambatipudi, Srikant ^{[1
,2
]}

Langdon, Ryan ^{[1
,2
]}

Richmond, Rebecca C. ^{[1
,2
]}

Suderman, Matthew ^{[1
,2
]}

Koestler, Devin C. ^{[3
]}

Kelsey, Karl T. ^{[4
,5
]}

Kazmi, Nabila ^{[1
,2
]}

Penfold, Christopher ^{[6
,7
]}

Ho, Karen M. ^{[2
]}

McArdle, Wendy ^{[2
]}

Ring, Susan M. ^{[1
,2
]}

Pring, Miranda ^{[6
,7
]}

Waterboer, Tim ^{[8
]}

Pawlita, Michael ^{[8
]}

Gaunt, Tom R. ^{[1
,2
]}

Smith, George Davey ^{[1
,2
]}

Thomas, Steve ^{[6
,7
]}

Ness, Andy R. ^{[6
,7
]}

Relton, Caroline L. ^{[1
,2
]}

机构：

[1] Univ Bristol, Bristol Med Sch, MRC Integrat Epidemiol Unit, Bristol, Avon, England

[2] Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England

[3] Univ Kansas, Med Ctr, Dept Biostat, Kansas City, KS 66103 USA

[4] Brown Univ, Dept Epidemiol, Sch Publ Hlth, Providence, RI 02912 USA

[5] Brown Univ, Dept Lab Med & Pathol, Providence, RI 02912 USA

[6] Univ Hosp Bristol NHS Fdn Trust, Bristol Biomed Res Ctr, NIHR, Bristol, Avon, England

[7] Univ Bristol, Bristol, Avon, England

[8] German Canc Res Ctr, Div Mol Diagnost Oncogen Infect, Infect Inflammat & Canc Program, Heidelberg, Germany

来源：

ORAL ONCOLOGY | 2018年 / 85卷

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

Head and neck cancer; Systemic inflammation; DNA methylation; Neutrophil-to-lymphocyte ratio; Lymphocyte-to-monocyte ratio; Overall survival; mdNLR; TO-LYMPHOCYTE RATIO; HUMAN-PAPILLOMAVIRUS; TUMOR MICROENVIRONMENT; ORAL-CAVITY; MECHANISMS; PROGNOSTICATORS; RESPONSES; SMOKING;

D O I：

10.1016/j.oraloncology.2018.08.021

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 x 10(-7)) while the converse was observed for mdLMR (OR = 0.88, 95% CI = 0.81-0.90, P = 2 x 10(-3)). In the HNSCC survival dataset, HPV16-E6 seropositive HNSCC cases had an elevated mdLMR (P = 9 x 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.

引用

页码：87 / 94

页数：8

共 61 条

[1] Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: Role of bone marrow-derived myelomonocytic cells [J].