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@ARTICLE{Yuan:291257,
      author       = {T. Yuan$^*$ and D. Wankhede$^*$ and D. Edelmann$^*$ 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        = {{L}arge-scale external validation and meta-analysis of gene
                      methylation biomarkers in tumor tissue for colorectal cancer
                      prognosis.},
      journal      = {EBioMedicine},
      volume       = {105},
      issn         = {2352-3964},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2024-01343},
      pages        = {105223},
      year         = {2024},
      note         = {#EA:C070#LA:C070#},
      abstract     = {DNA methylation biomarkers in colorectal cancer (CRC)
                      tissue hold potential as prognostic indicators. However,
                      individual studies have yielded heterogeneous results, and
                      external validation is largely absent. We conducted a
                      comprehensive external validation and meta-analysis of
                      previously suggested gene methylation biomarkers for CRC
                      prognosis.We performed a systematic search to identify
                      relevant studies investigating gene methylation biomarkers
                      for CRC prognosis until March 2024. Our external validation
                      cohort with long-term follow-up included 2303 patients with
                      CRC from 22 hospitals in southwest Germany. We used Cox
                      regression analyses to assess associations between
                      previously suggested gene methylation biomarkers and
                      prognosis, adjusting for clinical variables. We calculated
                      pooled hazard ratios (HRs) and their $95\%$ confidence
                      intervals (CIs) using random-effects models.Of 151 single
                      gene and 29 multiple gene methylation biomarkers identified
                      from 121 studies, 37 single gene and seven multiple gene
                      biomarkers were significantly associated with CRC prognosis
                      after adjustment for clinical variables. Moreover, the
                      directions of these associations with prognosis remained
                      consistent between the original studies and our validation
                      analyses. Seven single biomarkers and two multi-biomarker
                      signatures were significantly associated with CRC prognosis
                      in the meta-analysis, with a relatively strong level of
                      evidence for CDKN2A, WNT5A, MLH1, and EVL.In a comprehensive
                      evaluation of the so far identified gene methylation
                      biomarkers for CRC prognosis, we identified candidates with
                      potential clinical relevance for further investigation.The
                      German Research Council, the Interdisciplinary Research
                      Program of the National Center for Tumor Diseases (NCT),
                      Germany, the German Federal Ministry of Education and
                      Research.},
      keywords     = {Colorectal cancer (Other) / External validation (Other) /
                      Gene methylation biomarkers (Other) / Meta-analysis (Other)
                      / Prognosis (Other)},
      cin          = {C070 / C060 / W110 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)C060-20160331 /
                      I:(DE-He78)W110-20160331 / 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:38917511},
      doi          = {10.1016/j.ebiom.2024.105223},
      url          = {https://inrepo02.dkfz.de/record/291257},
}