Tumor DNA-methylome derived epigenetic fingerprint identifies HPV-negative head and neck patients at risk for locoregional recurrence after postoperative radiochemotherapy
Tawk B, Wirkner U, Schwager C, Rein K, Zaoui K, Federspil PA, Adeberg S, Linge A, Ganswindt U, Hess J, Unger K, Tinhofer I, Budach V, Lohaus F, Krause M, Guberina M, Stuschke M, Balermpas P, Rodel C, Grosu AL, Schaefer H, Zips D, Combs SE, Pigorsch S, Zitzelsberger H, Baumeister P, Kirchner T, Bewerunge-Hudler M, Weichert W, Hess J, Herpel E, Belka C, Baumann M, Debus J, Abdollahi A (2022)
Publication Type: Journal article
Publication year: 2022
Journal
Book Volume: 150
Pages Range: 603-616
Journal Issue: 4
DOI: 10.1002/ijc.33842
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.
Involved external institutions
Deutsches Krebsforschungszentrum (DKFZ)
Germany (DE)
Universitätsklinikum Heidelberg
Germany (DE)
LMU Klinikum
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Technische Universität Dresden
Germany (DE)
Germany (DE)
Universitätsklinikum Heidelberg
Germany (DE)
LMU Klinikum
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Technische Universität Dresden
Germany (DE)
How to cite
APA:
Tawk, B., Wirkner, U., Schwager, C., Rein, K., Zaoui, K., Federspil, P.A.,... Abdollahi, A. (2022). Tumor DNA-methylome derived epigenetic fingerprint identifies HPV-negative head and neck patients at risk for locoregional recurrence after postoperative radiochemotherapy. International Journal of Cancer, 150(4), 603-616. https://doi.org/10.1002/ijc.33842
MLA:
Tawk, Bouchra, et al. "Tumor DNA-methylome derived epigenetic fingerprint identifies HPV-negative head and neck patients at risk for locoregional recurrence after postoperative radiochemotherapy." International Journal of Cancer 150.4 (2022): 603-616.
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