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@ARTICLE{Qian:136923,
      author       = {J. Qian$^*$ and K. Tikk$^*$ and S. Werner$^*$ and Y.
                      Balavarca$^*$ and M. Saadati$^*$ and M. Hechtner$^*$ and H.
                      Brenner$^*$},
      title        = {{B}iomarker discovery study of inflammatory proteins for
                      colorectal cancer early detection demonstrated importance of
                      screening setting validation.},
      journal      = {Journal of clinical epidemiology},
      volume       = {104},
      issn         = {0895-4356},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2018-01360},
      pages        = {24 - 34},
      year         = {2018},
      abstract     = {Most studies identifying inflammatory markers for early
                      detection of colorectal cancer (CRC) were conducted using
                      clinically manifest cases. We aimed to identify circulating
                      inflammatory biomarkers for early detection of CRC and
                      validate them in both a clinical setting and a true
                      screening setting.A total of 92 inflammatory proteins were
                      quantified in baseline plasma samples from individuals
                      clinically diagnosed with CRC and neoplasm-free controls
                      matched on age and sex (training set). A multi-marker panel
                      was selected and evaluated in samples from another clinical
                      setting (validation set C) and a screening setting
                      (validation set S).In the training set (n=330) a 5-biomarker
                      signature was selected that provided an AUC of 0.85 and
                      $60.9\%$ sensitivity to detect CRC at $90\%$ specificity.
                      When this algorithm was applied to validation set C (n=318),
                      the AUC (0.80) and sensitivity $(49.5\%)$ at $90\%$
                      specificity for CRC diagnosis were only slightly lower than
                      those in the training set. In contrast, the diagnostic
                      performance of the algorithm in validation set S (n=126)
                      from a true screening setting was much poorer, with an AUC
                      of 0.59 and a sensitivity of $28.6\%$ at $90\%$
                      specificity.An inflammation-related protein panel with
                      apparently good diagnostic properties for CRC detection was
                      identified and confirmed in an independent clinical
                      validation set. However, the biomarker combination performed
                      substantially worse in a validation sample from a true
                      screening setting. Our results underline the importance of
                      validation in screening settings subsequently to novel
                      signature discovery for cancer early detection.},
      cin          = {C070 / G110 / C060 / L501 / L101},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)G110-20160331 /
                      I:(DE-He78)C060-20160331 / I:(DE-He78)L501-20160331 /
                      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:30076979},
      doi          = {10.1016/j.jclinepi.2018.07.016},
      url          = {https://inrepo02.dkfz.de/record/136923},
}