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@ARTICLE{Bhardwaj:147183,
      author       = {M. Bhardwaj$^*$ and A. Gies$^*$ and K. Weigl$^*$ and K.
                      Tikk and A. Benner$^*$ and P. Schrotz-King$^*$ and C. H.
                      Borchers and H. Brenner$^*$},
      title        = {{E}valuation and {V}alidation of {P}lasma {P}roteins
                      {U}sing {T}wo {D}ifferent {P}rotein {D}etection {M}ethods
                      for {E}arly {D}etection of {C}olorectal {C}ancer.},
      journal      = {Cancers},
      volume       = {11},
      number       = {10},
      issn         = {2072-6694},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2019-02319},
      pages        = {1426},
      year         = {2019},
      abstract     = {Plasma protein biomarkers could be an efficient alternative
                      for population-based screening for early detection of
                      colorectal cancer (CRC). The objective of this study was to
                      evaluate and validate plasma proteins individually and as a
                      signature for early detection of CRC.In a three-stage
                      design, proteins were measured firstly by liquid
                      chromatography/multiple reaction monitoring-mass
                      spectrometry (LC/MRM-MS) and later by proximity extension
                      assay (PEA) in a discovery set consisting of 96 newly
                      diagnosed CRC cases and 94 controls free of neoplasms at
                      screening colonoscopy. Two algorithms (one for each
                      measurement method) were derived by Lasso regression and
                      .632+ bootstrap based on 11 proteins that were included in
                      both the LC/MRM-MS and PEA measurements. Additionally,
                      another algorithm was constructed from the same eleven
                      biomarkers plus amphireglin, the most promising protein
                      marker in the PEA measurements that had not been available
                      from the LC/MRM-MS measurements. Lastly the three prediction
                      signatures were validated with PEA in independent samples of
                      participants of screening colonoscopy (CRC (n = 56),
                      advanced adenoma (n = 101), and participants free of
                      neoplasm (n = 102)).The same four proteins were included in
                      all three prediction signatures; mannan binding lectin
                      serine protease 1, osteopontin, serum paraoxonase lactonase
                      3 and transferrin receptor protein 1, and the third
                      prediction signature additionally included amphiregulin. In
                      the independent validation set from a true screening
                      setting, the five-marker blood-based signature including
                      AREG presented areas under the curves of 0.82 $(95\%$ CI,
                      0.74-0.89), 0.86 $(95\%$ CI, 0.77-0.92) and 0.76 $(95\%$ CI,
                      0.64-0.86) for all, early and late stages CRC,
                      respectively.Two different measurement methods consistently
                      identified four protein markers and an algorithm
                      additionally including amphiregulin, a marker measured by
                      PEA only, showed promising performance for detecting early
                      stage CRC in an independent validation in a true screening
                      setting. These proteins may be potential candidates for
                      blood-based tests for early detection of CRC.},
      cin          = {C120 / C070 / C060 / L101},
      ddc          = {610},
      cid          = {I:(DE-He78)C120-20160331 / I:(DE-He78)C070-20160331 /
                      I:(DE-He78)C060-20160331 / 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:31557860},
      doi          = {10.3390/cancers11101426},
      url          = {https://inrepo02.dkfz.de/record/147183},
}