%0 Journal Article
%A Tawk, Bouchra
%A Wirkner, Ute
%A Schwager, Christian
%A Rein, Katrin
%A Zaoui, Karim
%A Federspil, Philippe A
%A Adeberg, Sebastian
%A Linge, Annett
%A Ganswindt, Ute
%A Hess, Julia
%A Unger, Kristian
%A Tinhofer, Ingeborg
%A Budach, Volker
%A Lohaus, Fabian
%A Krause, Mechthild
%A Guberina, Maja
%A Stuschke, Martin
%A Balermpas, Panagiotis
%A Rödel, Claus
%A Grosu, Anca L
%A Schäfer, Henning
%A Zips, Daniel
%A Combs, Stephanie E
%A Pigorsch, Steffi
%A Zitzelsberger, Horst
%A Baumeister, Philipp
%A Kirchner, Thomas
%A Bewerunge-Hudler, Melanie
%A Weichert, Wilko
%A Hess, Jochen
%A Herpel, Esther
%A Belka, Claus
%A Baumann, Michael
%A Debus, Jürgen
%A Abdollahi, Amir
%T Tumor DNA-Methylome derived Epigenetic Fingerprint Identifies HPV-negative Head and Neck Patients at Risk for Locoregional Recurrence after Postoperative Radiochemotherapy.
%J International journal of cancer
%V 150
%N 4
%@ 0020-7136
%C Bognor Regis
%I Wiley-Liss
%M DKFZ-2021-02262
%P 603-616
%D 2022
%Z #EA:E210#LA:E210# / 2022 Feb 15;150(4):603-616
%X 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 HPVDNA 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 450K and 850K-EPIC microarray technology. The performance of the classifier was integrated with a series of biomarkers studied in 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 metastases 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. This article is protected by copyright. All rights reserved.
%K DNA Methylation (Other)
%K Disease Recurrence (Other)
%K Head and Neck Cancers (Other)
%K Radiotherapy (Other)
%K Stratification (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:34648658
%R 10.1002/ijc.33842
%U https://inrepo02.dkfz.de/record/177034