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