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| Home > Publications database > A tumor DNA-Methylome derived signature of Hypoxia Identifies HPV-negative head and neck cancer patients at risk for distant metastasis after postoperative radiochemotherapy (PORT-C). |
| Home > Publications database > A tumor DNA-Methylome derived signature of Hypoxia Identifies HPV-negative head and neck cancer patients at risk for distant metastasis after postoperative radiochemotherapy (PORT-C). |
| Journal Article | DKFZ-2026-00332 |
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2026
Elsevier Science
Amsterdam [u.a.]
Abstract: Tumor hypoxia is a predictive biomarker of treatment resistance in patients with head and neck squamous cell carcinoma (HNSCC). We previously reported the discovery of a tumor DNA methylation signature of hypoxia (Hypoxia-M), identifying HNSCC patients at risk for local recurrence (LR), all event progression, and death after primary radiochemotherapy (RCHT). We further validate Hypoxia-M in an independent cohort of HNSCC patients who underwent surgical resection followed by postoperative radiochemotherapy (PORT-C) METHODS: Hypoxia-M was validated in HPV-negative HNSCC patients (n = 134) homogeneously treated with PORT-C in the frame of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG) multicenter biomarker trial. DNA methylation was profiled using Illumina450K technology. The performance of Hypoxia-M was integrated with previously reported biomarkers, including gene expression signatures (GES) of hypoxia, a methylome-based HPV-Independent Classifier of disease Recurrence (HICR), and immune cell score using immunohistochemistry (CD3/CD8/PD-L1/PD1).Hypoxia-M was independently prognostic for overall survival (OS, HR = 2.34, p = 0.03) and distant metastasis (DM, HR = 4.3, p = 0.001), but not for LR after PORT-C. Hypoxia-M remained significant after adjusting for patientś age, gender, smoking status, tumor stage, and high-risk features (ECE&/R1 resection). Hypoxia-M status was inversely associated with CD8 T-cell infiltration. Patient stratification improved by integrating previously reported biomarkers, with Hypoxia-M demonstrating independent prognostic performance.The prognostic utility of Hypoxia-M was validated in an independent cohort. Our results highlighted a difference in recurrence patterns of hypoxic tumors treated in the primary setting (local recurrence) versus postoperatively (distant metastasis) and the utility of Hypoxia-M for identifying the main pattern of recurrence.
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