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000275441 245__ $$aDNA-Methylome based Tumor Hypoxia Classifier Identifies HPV-negative Head & Neck Cancer Patients at Risk for Locoregional Recurrence After Primary Radiochemotherapy.
000275441 260__ $$aPhiladelphia, Pa. [u.a.]$$bAACR$$c2023
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000275441 520__ $$aTumor hypoxia is a paradigmatic negative prognosticator of treatment resistance in Head and Neck Squamous Cell Carcinoma (HNSCC). The lack of robust and reliable hypoxia classifiers limits the adaptation of stratified therapies. We hypothesized that the tumor DNA methylation landscape might indicate epigenetic reprogramming induced by chronic intratumoral hypoxia.A DNA methylome-based tumor hypoxia classifier (Hypoxia-M) was trained in the TCGA-HNSCC cohort based on matched assignments using gene expression-based signatures of hypoxia (Hypoxia-GES). Hypoxia-M was validated in a multicenter DKTK-ROG trial consisting of Human Papilloma Virus (HPV)-negative HNSCC patients treated with primary radiochemotherapy (RCHT).While hypoxia-GSEs failed to stratify patients in the DKTK-ROG, Hypoxia-M was independently prognostic for local recurrence (LR, HR=4.3, p=0.001) and overall survival (OS, HR=2.34, p=0.03) but not distant metastasis (DM) after RCHT in the both cohorts. Hypoxia-M status was inversely associated with CD8 T-cells infiltration in both cohorts. Hypoxia-M was further prognostic in the TCGA-PanCancer cohort (HR=1.83, p=0.04), underscoring the breadth of this classifier for predicting tumor hypoxia status.Our findings highlight an unexplored avenue for DNA Methylation-based classifiers as biomarkers of tumoral hypoxia for identifying high-risk features in patients with HNSCC tumors.Retrospective observational study from the German Cancer Consortium (DKTK-ROG), not interventional.
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000275441 7001_ $$0P:(DE-He78)34ad9f967b71b1438cf5490a115c02d2$$aKnoll, Maximilian$$b3$$udkfz
000275441 7001_ $$0P:(DE-He78)f0fcac741a26b9e27398fe798a1138db$$aWirkner, Ute$$b4$$udkfz
000275441 7001_ $$0P:(DE-He78)c59ff25b48c192ed3fd4ad3a4bc9b9c0$$aHörner-Rieber, Juliane$$b5$$udkfz
000275441 7001_ $$00000-0002-1445-1940$$aLiermann, Jakob$$b6
000275441 7001_ $$0P:(DE-He78)f3723bca6eb95009d4c95a7590617b68$$aKurth, Ina$$b7$$udkfz
000275441 7001_ $$00000-0001-5261-6446$$aBalermpas, Panagiotis$$b8
000275441 7001_ $$00000-0001-7409-7093$$aRoedel, Claus$$b9
000275441 7001_ $$0P:(DE-He78)81b719227985a27b1b77ed6766094319$$aLinge, Annett$$b10$$udkfz
000275441 7001_ $$00000-0002-7017-3738$$aLoeck, Steffen$$b11
000275441 7001_ $$00000-0003-4043-7066$$aLohaus, Fabian$$b12
000275441 7001_ $$00000-0002-0512-549X$$aTinhofer, Ingeborg$$b13
000275441 7001_ $$0P:(DE-He78)4be9ccb23f3e472b97743845cd2b3fe9$$aKrause, Mechthild$$b14$$udkfz
000275441 7001_ $$00000-0001-6836-0940$$aStuschke, Martin$$b15
000275441 7001_ $$00000-0003-2255-2255$$aGrosu, Anca-Ligia$$b16
000275441 7001_ $$00000-0001-5779-9675$$aZips, Daniel$$b17
000275441 7001_ $$00000-0002-5233-1536$$aCombs, Stephanie E$$b18
000275441 7001_ $$00000-0002-1287-7825$$aBelka, Claus$$b19
000275441 7001_ $$00000-0003-1001-103X$$aStenzinger, Albrecht$$b20
000275441 7001_ $$aHerold-Mende, Christel$$b21
000275441 7001_ $$0P:(DE-He78)933f7d725ac87378f459623783585a1f$$aBaumann, Michael$$b22$$udkfz
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000275441 7001_ $$0P:(DE-He78)360c5bc2b71a849e35aca747c041dda7$$aAbdollahi, Amir$$b25$$eLast author$$udkfz
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