DNA-Methylome based Tumor Hypoxia Classifier Identifies HPV-negative Head & Neck Cancer Patients at Risk for Locoregional Recurrence After Primary Radiochemotherapy
Tumor hypoxia is a paradigmatic negative prognosticator of treatment resistance in Head and Neck Squamous Cell Carcinoma (HNSCC). The lack of robust and reliable hypoxia classifiers limits the adaptation of stratified therapies. We hypothesized that the tumor DNA methylation landscape might indicate epigenetic reprogramming induced by chronic intratumoral hypoxia.
A DNA methylome-based tumor hypoxia classifier (Hypoxia-M) was trained in the TCGA-HNSCC cohort based on matched assignments using gene expression-based signatures of hypoxia (Hypoxia-GES). Hypoxia-M was validated in a multicenter DKTK-ROG trial consisting of Human Papilloma Virus (HPV)-negative HNSCC patients treated with primary radiochemotherapy (RCHT).
While hypoxia-GSEs failed to stratify patients in the DKTK-ROG, Hypoxia-M was independently prognostic for local recurrence (LR, HR=4.3, p=0.001) and overall survival (OS, HR=2.34, p=0.03) but not distant metastasis (DM) after RCHT in the both cohorts. Hypoxia-M status was inversely associated with CD8 T-cells infiltration in both cohorts. Hypoxia-M was further prognostic in the TCGA-PanCancer cohort (HR=1.83, p=0.04), underscoring the breadth of this classifier for predicting tumor hypoxia status.
Our findings highlight an unexplored avenue for DNA Methylation-based classifiers as biomarkers of tumoral hypoxia for identifying high-risk features in patients with HNSCC tumors.
Retrospective observational study from the German Cancer Consortium (DKTK-ROG), not interventional.
Pharmacology, Toxicology and Pharmaceutical Science
3
25%
Biochemistry, Genetics and Molecular Biology
1
8%
Immunology and Microbiology
1
8%
Medicine and Dentistry
1
8%
Unknown
6
50%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 5. 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 26 August 2023.
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#9,379,301
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