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| Home > Publications database > Tumor DNA-Methylome derived Epigenetic Fingerprint Identifies HPV-negative Head and Neck Patients at Risk for Locoregional Recurrence after Postoperative Radiochemotherapy. |
| Home > Publications database > Tumor DNA-Methylome derived Epigenetic Fingerprint Identifies HPV-negative Head and Neck Patients at Risk for Locoregional Recurrence after Postoperative Radiochemotherapy. |
| Journal Article | DKFZ-2021-02262 |
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2022
Wiley-Liss
Bognor Regis
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Please use a persistent id in citations: doi:10.1002/ijc.33842 doi: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 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.
Keyword(s): DNA Methylation ; Disease Recurrence ; Head and Neck Cancers ; Radiotherapy ; Stratification
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