Research Papers:

PDCD1 (PD-1) promoter methylation predicts outcome in head and neck squamous cell carcinoma patients

Diane Goltz, Heidrun Gevensleben, Joern Dietrich, Friederike Schroeck, Luka de Vos, Freya Droege, Glen Kristiansen, Andreas Schroeck, Jennifer Landsberg, Friedrich Bootz and Dimo Dietrich _

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Oncotarget. 2017; 8:41011-41020. https://doi.org/10.18632/oncotarget.17354

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Diane Goltz1,*, Heidrun Gevensleben2,*, Joern Dietrich3, Friederike Schroeck3, Luka de Vos3, Freya Droege4, Glen Kristiansen2, Andreas Schroeck3, Jennifer Landsberg5, Friedrich Bootz3 and Dimo Dietrich3

1Institute of Pathology, University Hospital Cologne, Cologne, Germany

2Institute of Pathology, University Hospital Bonn, Bonn, Germany

3Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Bonn, Germany

4Ear, Nose and Throat Clinic, University Hospital Essen, Essen, Germany

5Department of Dermatology and Allergy, University of Bonn, Bonn, Germany

*These authors contributed equally to this work

Correspondence to:

Dimo Dietrich, email: [email protected]

Keywords: PD-1, PDCD1, HPV, head and neck squamous cell carcinoma, DNA methylation

Received: March 02, 2017     Accepted: April 11, 2017     Published: April 21, 2017


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.

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