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dc.contributor.authorKostareli, Efterpien
dc.contributor.authorHielscher, Thomasen
dc.contributor.authorZucknick, Manuelaen
dc.contributor.authorBaboci, Lorenaen
dc.contributor.authorWichmann, Gunnaren
dc.contributor.authorHolzinger, Danaen
dc.contributor.authorMücke, Oliveren
dc.contributor.authorPawlita, Michaelen
dc.contributor.authorDel Mistro, Annarosaen
dc.contributor.authorBoscolo-Rizzo, Paoloen
dc.contributor.authorDa Mosto, Maria Cristinaen
dc.contributor.authorTirelli, G.en
dc.contributor.authorPlinkert, Peteren
dc.contributor.authorDietz, Andreasen
dc.contributor.authorPlass, Christophen
dc.contributor.authorWeichenhan, Dieteren
dc.contributor.authorHess, Jochenen
dc.date.accessioned2017-09-20T13:38:15Z
dc.date.available2017-09-20T13:38:15Z
dc.date.issued2016-01-19
dc.identifier.citationKostareli, E. et al. (2016) Gene promoter methylation signature predicts survival of head and neck squamous cell carcinoma patients. Epigenetics, 11 (1), pp. 61-73en
dc.identifier.urihttp://hdl.handle.net/2086/14521
dc.descriptionProject was completed in previous post, I joined DMU on 01/01/2016en
dc.description.abstractInfection with high-risk types of human papilloma virus (HPV) is currently the best-established prognostic marker for head and neck squamous cell carcinoma (HNSCC), one of the most common and lethal human malignancies worldwide. Clinical trials have been launched to address the concept of treatment de-escalation for HPV-positive HNSCC with the final aim to reduce treatment related toxicity and debilitating long-term impacts on the quality of life. However, HPV-related tumors are mainly restricted to oropharyngeal SCC (OPSCC) and there is an urgent need to establish reliable biomarkers for all patients at high risk for treatment failure. A patient cohort (n = 295) with mainly non-OPSCC (72.9%) and a low prevalence of HPV16-related tumors (8.8%) was analyzed by MassARRAY to determine a previously established prognostic methylation score (MS). Kaplan-Meier revealed a highly significant correlation between a high MS and a favorable survival for OPSCC (P = 0.0004) and for non-OPSCC (P<0.0001), which was confirmed for all HNSCC by multivariate Cox regression models (HR: 9.67, 95% CI [4.61-20.30], P<0.0001). Next, we established a minimal methylation signature score (MMSS), which consists of ten most informative of the originally 62 CpG units used for the MS. The prognostic value of the MMSS was confirmed by Kaplan-Meier analysis for all HNSCC (P<0.0001) and non-OPSCC (P = 0.0002), and was supported by multivariate Cox regression models for all HNSCC (HR: 2.15, 95% CI [1.36-3.41], P = 0.001). In summary, the MS and the MMSS exhibit an excellent performance as prognosticators for survival, which is not limited by the anatomical site, and both could be implemented in future clinical trials.en
dc.language.isoenen
dc.publisherTaylor and Francisen
dc.subjectDNA methylationen
dc.subjectHNSCCen
dc.subjectHPVen
dc.subjectMassARRAYen
dc.subjectOPSCCen
dc.subjecthead and neck canceren
dc.subjectsquamous cell carcinomaen
dc.titleGene promoter methylation signature predicts survival of head and neck squamous cell carcinoma patients.en
dc.typeArticleen
dc.identifier.doihttp://dx.doi.org/10.1080/15592294.2015.1137414
dc.peerreviewedYesen
dc.funderHeidelberg University, Medical Facultyen
dc.projectidN/Aen
dc.cclicenceN/Aen
dc.date.acceptance2016-01-18en


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