TY  - JOUR
AU  - Tawk, Bouchra
AU  - Wirkner, Ute
AU  - Schwager, Christian
AU  - Rein, Katrin
AU  - Zaoui, Karim
AU  - Federspil, Philippe A
AU  - Adeberg, Sebastian
AU  - Linge, Annett
AU  - Ganswindt, Ute
AU  - Hess, Julia
AU  - Unger, Kristian
AU  - Tinhofer, Ingeborg
AU  - Budach, Volker
AU  - Lohaus, Fabian
AU  - Krause, Mechthild
AU  - Guberina, Maja
AU  - Stuschke, Martin
AU  - Balermpas, Panagiotis
AU  - Rödel, Claus
AU  - Grosu, Anca L
AU  - Schäfer, Henning
AU  - Zips, Daniel
AU  - Combs, Stephanie E
AU  - Pigorsch, Steffi
AU  - Zitzelsberger, Horst
AU  - Baumeister, Philipp
AU  - Kirchner, Thomas
AU  - Bewerunge-Hudler, Melanie
AU  - Weichert, Wilko
AU  - Hess, Jochen
AU  - Herpel, Esther
AU  - Belka, Claus
AU  - Baumann, Michael
AU  - Debus, Jürgen
AU  - Abdollahi, Amir
TI  - Tumor DNA-Methylome derived Epigenetic Fingerprint Identifies HPV-negative Head and Neck Patients at Risk for Locoregional Recurrence after Postoperative Radiochemotherapy.
JO  - International journal of cancer
VL  - 150
IS  - 4
SN  - 0020-7136
CY  - Bognor Regis
PB  - Wiley-Liss
M1  - DKFZ-2021-02262
SP  - 603-616
PY  - 2022
N1  - #EA:E210#LA:E210# / 2022 Feb 15;150(4):603-616
AB  - 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.
KW  - DNA Methylation (Other)
KW  - Disease Recurrence (Other)
KW  - Head and Neck Cancers (Other)
KW  - Radiotherapy (Other)
KW  - Stratification (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34648658
DO  - DOI:10.1002/ijc.33842
UR  - https://inrepo02.dkfz.de/record/177034
ER  -