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@ARTICLE{Yuan:300747,
      author       = {T. Yuan$^*$ and D. Edelmann$^*$ and V. Moreno and E.
                      Georgii and L. B. de Andrade E Sousa and H. Pelin and X.
                      Jiang and J. N. Kather and K. E. Tagscherer and W. Roth and
                      M. Bewerunge-Hudler$^*$ and A. Brobeil and M. Kloor and H.
                      Bläker and H. Brenner$^*$ and M. Hoffmeister$^*$},
      title        = {{I}dentification and external validation of tumor {DNA}
                      methylation panel for the recurrence risk stratification of
                      stage {II} colon cancer.},
      journal      = {Translational oncology},
      volume       = {57},
      issn         = {1944-7124},
      address      = {Ann Arbor, Mich.},
      publisher    = {[Verlag nicht ermittelbar]},
      reportid     = {DKFZ-2025-00907},
      pages        = {102405},
      year         = {2025},
      note         = {#EA:C070#LA:C070#},
      abstract     = {Tailoring surveillance and treatment strategies for stage
                      II colon cancer (CC) after curative surgery remains
                      challenging, and personalized approaches are lacking. We
                      aimed to identify a gene methylation panel capable of
                      stratifying high-risk stage II CC patients for recurrence
                      beyond traditional clinical variables.Genome-wide tumor
                      tissue DNA methylation data were analyzed from 562 stage II
                      CC patients who underwent surgery in Germany (DACHS study).
                      The cohort was divided into a training set (N = 395) and an
                      internal validation set (N = 131), with external validation
                      performed on 97 stage II CC patients from Spain. DNA
                      methylation markers were primarily selected using the
                      Elastic Net Cox model. The resulting prognostic index (PI),
                      a combination of clinical factors and selected methylation
                      markers, was compared to baseline models using clinical
                      variables or microsatellite instability (MSI), with
                      discrimination and prediction accuracy assessed through
                      time-dependent receiver operating characteristic curves
                      (AUC) and Brier scores.The final PI incorporated age, sex,
                      tumor stage, location, and 27 DNA methylation markers. The
                      PI consistently outperformed the baseline model including
                      age, sex, and tumor stage in time-dependent AUC across
                      validation cohorts (e.g., 1-year AUC and 95 $\%$ confidence
                      interval: internal validation set, PI: 0.66, baseline model:
                      0.52; external validation set, PI: 0.72, baseline model:
                      0.64). In internal validation, the PI also showed a
                      consistently improved time-dependent AUC compared with a
                      combination of MSI and tumor stage only. Nevertheless, the
                      PI did not improve the prediction accuracy of CC recurrence
                      compared to the baseline model.This study identified 27
                      tumor tissue DNA methylation biomarkers that improved the
                      discriminative power in classifying recurrence risk among
                      stage II colon cancer patients. While this methylation panel
                      alone lacks sufficient prediction accuracy for clinical
                      application, its discriminative improvement suggests
                      potential value as part of a multimodal risk-stratification
                      tool.},
      keywords     = {Colon cancer (Other) / DNA methylation panel (Other) /
                      Prognostic index (Other) / Recurrence risk (Other)},
      cin          = {C060 / W110 / C070 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)C060-20160331 / I:(DE-He78)W110-20160331 /
                      I:(DE-He78)C070-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40311420},
      doi          = {10.1016/j.tranon.2025.102405},
      url          = {https://inrepo02.dkfz.de/record/300747},
}