Tumor DNA‐methylome derived epigenetic fingerprint identifies HPV‐negative head and neck patients at risk for locoregional recurrence after postoperative radiochemotherapy
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.
Pharmacology, Toxicology and Pharmaceutical Science
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Nursing and Health Professions
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Other
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Unknown
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Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 October 2021.
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