PITX2andPANCRDNA methylation predicts overall survival in patients with head and neck squamous cell carcinoma

// Verena Sailer 1, 2, * , Emily Eva Holmes 3, * , Heidrun Gevensleben 3 , Diane Goltz 3 , Freya Dröge 4 , Luka de Vos 6 , Alina Franzen 6 , Friederike Schröck 5 , Friedrich Bootz 6 , Glen Kristiansen 3 , Andreas Schröck 6, † , Dimo Dietrich 3, 6, † 1 Weill Medical College of Cornell University and New York Presbyterian Hospital, Department of Pathology and Laboratory Medicine, New York, NY, USA 2 Weill Medical College of Cornell University and New York Presbyterian Hospital, Englander Institute for Precision Medicine, New York, NY, USA 3 Institute of Pathology, University Hospital of Bonn, Bonn, Germany 4 Department of Otorhinolaryngology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany 5 Department of Addictive Disorders and Addiction Medicine, LVR Hospital Bonn, Bonn, Germany 6 University 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 Correspondence to: Dimo Dietrich, email: dimo.dietrich@gmail.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 ABSTRACT 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.