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@ARTICLE{Kostareli:128951,
      author       = {E. Kostareli and T. Hielscher$^*$ and M. Zucknick and L.
                      Baboci$^*$ and G. Wichmann and D. Holzinger$^*$ and O.
                      Mücke and M. Pawlita$^*$ and A. Del Mistro and P.
                      Boscolo-Rizzo and M. C. Da Mosto and G. Tirelli and P.
                      Plinkert and A. Dietz and C. Plass$^*$ and D. Weichenhan$^*$
                      and J. Hess$^*$},
      title        = {{G}ene promoter methylation signature predicts survival of
                      head and neck squamous cell carcinoma patients.},
      journal      = {Epigenetics},
      volume       = {11},
      number       = {1},
      issn         = {1559-2308},
      address      = {Austin, Tex.},
      publisher    = {Landes Bioscience},
      reportid     = {DKFZ-2017-04963},
      pages        = {61 - 73},
      year         = {2016},
      abstract     = {Infection 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.},
      keywords     = {Biomarkers, Tumor (NLM Chemicals)},
      cin          = {F020 / C010 / G405 / C060},
      ddc          = {610},
      cid          = {I:(DE-He78)F020-20160331 / I:(DE-He78)C010-20160331 /
                      I:(DE-He78)G405-20160331 / I:(DE-He78)C060-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:26786582},
      pmc          = {pmc:PMC4846111},
      doi          = {10.1080/15592294.2015.1137414},
      url          = {https://inrepo02.dkfz.de/record/128951},
}