Online citations, reference lists, and bibliographies.

PDCD1 (PD-1) Promoter Methylation Predicts Outcome In Head And Neck Squamous Cell Carcinoma Patients

Diane Goltz, Heidrun Gevensleben, Joern Dietrich, Friederike Schröck, Luka de Vos, Freya Droege, Glen Kristiansen, Andreas Schroeck, Jennifer Landsberg, Friedrich Bootz, Dimo Dietrich
Published 2017 · Medicine
Cite This
Download PDF
Analyze on Scholarcy
Background Biomarkers that facilitate the prediction of disease recurrence in head and neck squamous cell carcinoma (HNSCC) may enable physicians to personalize treatment. In the current study, DNA promoter methylation of programmed cell death 1 (PDCD1, PD-1) was evaluated as a prognostic biomarker in HNSCC patients. Results High PDCD1 methylation (mPDCD1) was associated with a significantly shorter overall survival after surgical resection in both the discovery (HR = 2.24 [95%CI: 1.08–4.64], p = 0.029) and the validation cohort (HR = 1.54 [95%CI: 1.08–2.21], p = 0.017). In multivariate Cox proportional hazards analysis, PDCD1 methylation remained a significant prognostic factor for HNSCC (HR = 2.14 [95%CI: 1.19–3.84], p = 0.011). Further, mPDCD1 was strongly associated with the human papilloma virus (HPV) status. Materials and Methods mPDCD1 was assessed retrospectively in a discovery cohort of 120 HNSCC patients treated at the University Hospital of Bonn and a validation cohort of 527 HNSCC cases analyzed by The Cancer Genome Atlas Research Network. Conclusions PDCD1 methylation might aid the identification of HNSCC patients potentially benefitting from a radical or alternative treatment, particularly in the context of immunotherapies targeting PD-1/PD-L1.
This paper references
Chronic virus infection enforces demethylation of the locus that encodes PD-1 in antigenspecific
B Youngblood (2011)
The molecular biology of head and neck cancer
C. René Leemans (2011)
Eurogin Roadmap: comparative epidemiology of HPV infection and associated cancers of the head and neck and cervix.
Maura L. Gillison (2014)
The alternative role of DNA methylation in splicing regulation.
Galit Lev Maor (2015)
PD - L 1 ( CD 274 ) promoter methylation predicts survival in patients with acute myeloid
H Gevensleben (2017)
Gene promoter methylation signature predicts survival of head and neck squamous cell carcinoma patients
Efterpi Kostareli (2016)
Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC): Pooled analyses after long-term follow-up in KEYNOTE-012.
Ranee Mehra (2016)
Epigenetic modification of the PD-1 (Pdcd1) promoter in effector CD4+ T cells tolerized by peptide immunotherapy
Rhoanne C. McPherson (2014)
Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer
James A. Stockman (2012)
Chronic virus infection enforces demethylation of the locus that encodes PD-1 in antigen-specific CD8(+) T cells.
B. J. Youngblood (2011)
PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer.
Cécile Badoual (2013)
Promoter methylation of the immune checkpoint receptor PD-1 (PDCD1) is an independent prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy
Diane Goltz (2016)
Head and neck carcinoma in the United States: first comprehensive report of the Longitudinal Oncology Registry of Head and Neck Carcinoma (LORHAN).
K. Ang (2012)
Immunotherapy for head and neck squamous cell carcinoma
Thorsten Fuereder (2016)
The blockade of immune checkpoints in cancer immunotherapy
D. Pardoll (2012)
American Cancer Society Head and Neck Cancer Survivorship Care Guideline.
Ezra E. W. Cohen (2016)
The Path to Reactivation of Antitumor Immunity and Checkpoint Immunotherapy
Hye-Jung Kim (2014)
PD-L1 (CD274) promoter methylation predicts survival in patients with acute myeloid leukemia
Diane Goltz (2017)
Head and neck carcinoma in the United States: first comprehensive report of the Longitudinal Oncology Registry of Head and Neck Carcinoma
KK Ang (2012)
Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy
S. Topalian (2016)
PD-1 blockade attenuates immunosuppressive myeloid cells due to inhibition of CD47/SIRPα axis in HPV negative head and neck squamous cell carcinoma
G. Yu (2015)
Development and clinical validation of a real-time PCR assay for PITX2 DNA methylation to predict prostate-specific antigen recurrence in prostate cancer patients following radical prostatectomy.
Dimo Dietrich (2013)
PD-L1 promoter methylation is a prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy
Heidrun Gevensleben (2016)
The PD-1 pathway in tolerance and autoimmunity.
Loise M. Francisco (2010)
Comprehensive analyses of tumor immunity: implications for cancer immunotherapy
Bo Li (2016)
The Genomics, Epigenomics, and Transcriptomics of HPV-Associated Oropharyngeal Cancer--Understanding the Basis of a Rapidly Evolving Disease.
Matthias Lechner (2016)
Performance Evaluation of Kits for Bisulfite-Conversion of DNA from Tissues, Cell Lines, FFPE Tissues, Aspirates, Lavages, Effusions, Plasma, Serum, and Urine
Emily Eva Holmes (2014)
Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma.
Sofia Lyford-Pike (2013)
Cancer Risk Associated with Alcohol and Tobacco Use: Focus on Upper Aero-digestive Tract and Liver
C. Pelucchi (2006)
Functions of DNA methylation: islands, start sites, gene bodies and beyond
Peter A. Jones (2012)
The search for infectious causes of human cancers: where and why (Nobel lecture).
H zurHausen (2009)
Notes on the role of dynamic DNA methylation in mammalian development
T. Bestor (2014)
Evidence for a causal association between human papillomavirus and a subset of head and neck cancers.
M. Gillison (2000)
Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results From the Phase Ib KEYNOTE-012 Expansion Cohort
Laura Quan Man Chow (2016)
Papillomaviruses and cancer: from basic studies to clinical application
H. Hausen (2002)
Gene Expression Differences Associated with Human Papillomavirus Status in Head and Neck Squamous Cell Carcinoma
R. Slebos (2006)

This paper is referenced by
Epigenetic regulators of programmed death‐ligand 1 expression in human cancers
S. Kumar (2018)
Detailed analysis of adenosine A2a receptor (ADORA2A) and CD73 (5′-nucleotidase, ecto, NT5E) methylation and gene expression in head and neck squamous cell carcinoma patients
Timo J. Vogt (2018)
Clinicopathological, immune and molecular correlates of PD-L2 methylation in gastric adenocarcinomas.
Philipp Lingohr (2019)
Comprehensive analysis of tumor necrosis factor receptor TNFRSF9 (4-1BB) DNA methylation with regard to molecular and clinicopathological features, immune infiltrates, and response prediction to immunotherapy in melanoma
Anne Froehlich (2020)
miR-134 targets PDCD7 to reduce E-cadherin expression and enhance oral cancer progression.
Shih-Yuan Peng (2018)
PD-1 (PDCD1) Promoter Methylation Is a Prognostic Factor in Patients With Diffuse Lower-Grade Gliomas Harboring Isocitrate Dehydrogenase (IDH) Mutations
Lea Kristin Röver (2018)
PD-1 (PDCD1) promoter methylation in Merkel cell carcinoma: prognostic relevance and relationship with clinico-pathological parameters
C. Ricci (2019)
Role of Epigenetic Modifications in Inhibitory Immune Checkpoints in Cancer Development and Progression
Reem Saleh (2020)
Head and neck squamous cell carcinoma: Genomics and emerging biomarkers for immunomodulatory cancer treatments.
Benjamin J. Solomon (2018)
Prognostic Impact of MCPyV and TIL Subtyping in Merkel Cell Carcinoma: Evidence from a Large European Cohort of 95 Patients
C. Ricci (2019)
Omics-wide quantitative B-cell infiltration analyses identify GPR18 for human cancer prognosis with superiority over CD20
Yuchen Liu (2020)
PD-L1 (CD274) and PD-L2 (PDCD1LG2) promoter methylation is associated with HPV infection and transcriptional repression in head and neck squamous cell carcinomas
Alina Franzen (2018)
The Landscape of CD28, CD80, CD86, CTLA4, and ICOS DNA Methylation in Head and Neck Squamous Cell Carcinomas.
Luka de Vos (2020)
DNA methylation of indoleamine 2,3-dioxygenase 1 (IDO1) in head and neck squamous cell carcinomas correlates with IDO1 expression, HPV status, patients’ survival, immune cell infiltrates, mutational load, and interferon γ signature
Verena Sailer (2019)
Regulation of PD-L1 expression in cancer and clinical implications in immunotherapy.
Xiaoli Ju (2020)
PD-L1 methylation regulates PD-L1 expression and is associated with melanoma survival.
Goran Micevic (2019)
Epigenetics, a key player of immunotherapy resistance
Paul Peixoto (2018)
LAG3 (LAG-3, CD223) DNA methylation correlates with LAG3 expression by tumor and immune cells, immune cell infiltration, and overall survival in clear cell renal cell carcinoma
Niklas Klümper (2020)
Semantic Scholar Logo Some data provided by SemanticScholar