Tumor DNA‐methylome derived epigenetic fingerprint identifies HPV ‐negative head and neck patients at risk for locoregional recurrence after postoperative radiochemotherapy
Year: 2021
Type: article
Abstract: Biomarkers with relevance for loco‐regional therapy are needed in human papillomavirus negative aka HPV(−) head and neck squamous cell carcinoma (HNSCC). Based on the premise that DNA methylation pattern is highly conserved, we sought to develop a reliable and robust methylome‐based classifier identifying HPV(−) HNSCC patients at risk for loco‐regional recurrence (LR) and all‐event progression after postoperative radiochemotherapy (PORT‐C). The training cohort consisted of HPV‐DNA negative HNSCC patients (n = 128) homogeneously treated with PORT‐C in frame of the German Cancer Consortium—Radiation Oncology Group (DKTK‐ROG) multicenter biomarker trial. DNA Methylation analysis was performed using Illumina 450 K and 850 K‐EPIC microarray technology. The performance of the classifier was integrated with a series of biomarkers studied in the training set namely hypoxia‐, 5‐microRNA (5‐miR), stem‐cell gene‐expression signatures and immunohistochemistry (IHC)‐based immunological characterization of tumors (CD3/CD8/PD‐L1/PD1). Validation occurred in an independent cohort of HPV(−) HNSCC patients, pooled from two German centers (n = 125). We identified a 38‐methylation probe‐based HPV(−) Independent Classifier of disease Recurrence (HICR) with high prognostic value for LR, distant metastasis and overall survival (P < 10−9). HICR remained significant after multivariate analysis adjusting for anatomical site, lymph node extracapsular extension (ECE) and size (T‐stage). HICR high‐risk tumors were enriched for younger patients with hypoxic tumors (15‐gene signature) and elevated 5‐miR score. After adjustment for hypoxia and 5‐miR covariates, HICR maintained predicting all endpoints. HICR provides a novel mean for assessing the risk of LR in HPV(−) HNSCC patients treated with PORT‐C and opens a new opportunity for biomarker‐assisted stratification and therapy adaptation in these patients.
Source: International Journal of Cancer
DOI: 10.1002/ijc.33842
Authors: Bouchra Tawk, Ute Wirkner, Christian Schwager, Katrin Rein, Karim Zaoui, Philippe A. Federspil, Sebastian Adeberg, Annett Linge, Ute Ganswindt, Julia Hess, Kristian Unger, Ingeborg Tinhofer, Volker Budach, Fabian Lohaus, Mechthild Krause, Maja Guberina, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Anca L. Grosu, Henning Schäfer, Daniel Zips, Stephanie E. Combs, Steffi Pigorsch, Horst Zitzelsberger, Philipp Baumeister, Thomas Kirchner, Melanie Bewerunge‐Hudler, Wilko Weichert, Jochen Hess, Esther Herpel, Claus Belka, Michael Baumann, Jürgen Debus, Amir Abdollahi, For the DKTK‐ROG
Institutions: German Cancer Research Center, Heidelberg University, University Hospital Heidelberg, National Center for Tumor Diseases, Deutsches Konsortium für Translationale Krebsforschung, Heidelberger Institut für Radioonkologie, OncoRay, University Hospital Carl Gustav Carus, Nationales Centrum für Tumorerkrankungen Dresden, German Cancer Consortium (DKTK) Dresden, Technische Universität Dresden, Innsbruck Medical University, Universität Innsbruck, Helmholtz Munich, Ludwig-Maximilians-Universität München, Charité – Universitätsmedizin Berlin, University of Duisburg-Essen, University Hospital Zurich, Goethe University Frankfurt, University of Freiburg, University Medical Center Freiburg, University of Tübingen, Technical University of Munich, Pathologisches Institut
Language: English
Topic: Head and Neck Cancer Studies
Subfield: Otorhinolaryngology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,600
OpenAlex ID: W3205991001