PITX2 and PANCR DNA methylation predicts overall survival in patients with head and neck squamous cell carcinoma
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Verena Sailer1,2,*, Emily Eva Holmes3,*, Heidrun Gevensleben3, Diane Goltz3, Freya Dröge4, Luka de Vos6, Alina Franzen6, Friederike Schröck5, Friedrich Bootz6, Glen Kristiansen3, Andreas Schröck6,†, Dimo Dietrich3,6,†
1Weill Medical College of Cornell University and New York Presbyterian Hospital, Department of Pathology and Laboratory Medicine, New York, NY, USA
2Weill Medical College of Cornell University and New York Presbyterian Hospital, Englander Institute for Precision Medicine, New York, NY, USA
3Institute of Pathology, University Hospital of Bonn, Bonn, Germany
4Department of Otorhinolaryngology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
5Department of Addictive Disorders and Addiction Medicine, LVR Hospital Bonn, Bonn, Germany
6University Hospital Bonn, Department of Otolaryngology, Head and Neck Surgery, Bonn, Germany
*These authors have contributed equally to this work
†These authors are joined senior authors on this work
Dimo Dietrich, email: email@example.com
Keywords: PITX2, biomarker, head and neck squamous cell carcinoma, DNA methylation, PANCR
Received: July 25, 2016 Accepted: September 20, 2016 Published: October 3, 2016
Background: Squamous cell carcinoma of the head and neck region (HNSCC) is a common malignant disease accompanied by a high risk of local or distant recurrence after curative-intent treatment. Biomarkers that allow for the prediction of disease outcome can guide clinicians with respect to treatment and surveillance strategies. Here, the methylation status of PITX2 and an adjacent lncRNA (PANCR) were evaluated for their ability to predict overall survival in HNSCC patients.
Results: PITX2 hypermethylation was associated with a better overall survival (hazard ratio, HR = 0.51, 95%CI: 0.35-0.74, p<0.001), while PANCR hypermethylation was significantly associated with an increased risk of death (HR = 1.64, 95%CI: 1.12-2.39, p=0.010).
Methods: Quantitative, methylation-specific real-time PCR assays for PITX2 and PANCR were employed to measure bisulfite-converted DNA from formalin-fixed, paraffin-embedded (FFPE) tissues in a cohort of 399 patients with localized or locally advanced HNSCC who received curative-intent treatment (surgery with optional adjuvant radiochemotherapy or definite radiochemotherapy).
Conclusions: PITX2 and PANCR methylation status were shown to be independent predictors for overall survival in HNSCC patients. Tissue-based methylation testing could therefore potentially be employed to identify patients with a high risk for death who might benefit from a more radical or alternative treatment.
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