Journal Article

DKFZ-2023-00764

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png DNA-Methylome based Tumor Hypoxia Classifier Identifies HPV-negative Head & Neck Cancer Patients at Risk for Locoregional Recurrence After Primary Radiochemotherapy.

Tawk, B. (First author)DKFZ* ; Rein, K.DKFZ* ; Schwager, C.DKFZ* ; Knoll, M.DKFZ* ; Wirkner, U.DKFZ* ; Hörner-Rieber, J.DKFZ* ; Liermann, J.DKFZ* ; Kurth, I.DKFZ* ; Balermpas, P.DKFZ* ; Roedel, C.DKFZ* ; Linge, A.DKFZ* ; Loeck, S.DKFZ* ; Lohaus, F.DKFZ* ; Tinhofer, I.DKFZ* ; Krause, M.DKFZ* ; Stuschke, M.DKFZ* ; Grosu, A.-L.DKFZ* ; Zips, D.DKFZ* ; Combs, S. E.DKFZ* ; Belka, C.DKFZ* ; Stenzinger, A.DKFZ* ; Herold-Mende, C. ; Baumann, M.DKFZ* ; Schirmacher, P.DKFZ* ; Debus, J.DKFZ* ; Abdollahi, A. (Last author)DKFZ*

2023
AACR Philadelphia, Pa. [u.a.]

This record in other databases:  

Please use a persistent id in citations: doi:10.1158/1078-0432.CCR-22-3790

Abstract: 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.

Note: #EA:E210#LA:E210# / 2023 Aug 15;29(16):3051-3064

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Contributing Institute(s):

1. E210 KKE Translationale Radioonkologie (E210)
2. E050 KKE Strahlentherapie (E050)
3. DKTK Koordinierungsstelle Dresden (DD01)
4. DKTK Koordinierungsstelle Frankfurt (FM01)
5. DKTK Koordinierungsstelle Berlin (BE01)
6. DKTK Koordinierungsstelle Essen/Düsseldorf (ED01)
7. DKTK Koordinierungsstelle Freiburg (FR01)
8. DKTK Koordinierungsstelle Tübingen (TU01)
9. DKTK Koordinierungsstelle München (MU01)
10. E220 Radioonkologie Radiobiologie (E220)
11. DKTK HD zentral (HD01)

Research Program(s):

1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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