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@ARTICLE{Gndert:142868,
      author       = {M. Gündert$^*$ and D. Edelmann$^*$ and A. Benner$^*$ and
                      L. Jansen$^*$ and M. Jia$^*$ and V. Walter$^*$ and P. Knebel
                      and E. Herpel and J. Chang-Claude$^*$ and M. Hoffmeister$^*$
                      and H. Brenner$^*$ and B. Burwinkel$^*$},
      title        = {{G}enome-wide {DNA} methylation analysis reveals a
                      prognostic classifier for non-metastatic colorectal cancer
                      ({P}ro{MC}ol classifier).},
      journal      = {Gut},
      volume       = {68},
      number       = {1},
      issn         = {1468-3288},
      address      = {London},
      publisher    = {BMJ Publishing Group},
      reportid     = {DKFZ-2019-00498},
      pages        = {101 - 110},
      year         = {2019},
      abstract     = {Pathological staging used for the prediction of patient
                      survival in colorectal cancer (CRC) provides only limited
                      information.Here, a genome-wide study of DNA methylation was
                      conducted for two cohorts of patients with non-metastatic
                      CRC (screening cohort (n=572) and validation cohort
                      (n=274)). A variable screening for prognostic CpG sites was
                      performed in the screening cohort using marginal testing
                      based on a Cox model and subsequent adjustment of the
                      p-values via independent hypothesis weighting using the
                      methylation difference between 34 pairs of tumour and normal
                      mucosa tissue as auxiliary covariate. From the 1000 CpG
                      sites with the smallest adjusted p-value, 20 CpG sites with
                      the smallest Brier score for overall survival (OS) were
                      selected. Applying principal component analysis, we derived
                      a prognostic methylation-based classifier for patients with
                      non-metastatic CRC (ProMCol classifier).This classifier was
                      associated with OS in the screening (HR 0.51, $95\%$ CI 0.41
                      to 0.63, p=6.2E-10) and the validation cohort (HR 0.61,
                      $95\%$ CI 0.45 to 0.82, p=0.001). The independent validation
                      of the ProMCol classifier revealed a reduction of the
                      prediction error for 3-year OS from 0.127, calculated only
                      with standard clinical variables, to 0.120 combining the
                      clinical variables with the classifier and for 4-year OS
                      from 0.153 to 0.140. All results were confirmed for
                      disease-specific survival.The ProMCol classifier could
                      improve the prognostic accuracy for patients with
                      non-metastatic CRC.},
      cin          = {C080 / C060 / C070 / C020 / C120 / L101},
      ddc          = {610},
      cid          = {I:(DE-He78)C080-20160331 / I:(DE-He78)C060-20160331 /
                      I:(DE-He78)C070-20160331 / I:(DE-He78)C020-20160331 /
                      I:(DE-He78)C120-20160331 / I:(DE-He78)L101-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29101262},
      doi          = {10.1136/gutjnl-2017-314711},
      url          = {https://inrepo02.dkfz.de/record/142868},
}