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@ARTICLE{Wagner:127733,
      author       = {N. B. Wagner$^*$ and B. Weide and M. Reith$^*$ and K.
                      Tarnanidis$^*$ and C. Kehrel$^*$ and R. Lichtenberger$^*$
                      and A. Pflugfelder and E. Herpel and J. Eubel and K.
                      Ikenberg and C. Busch and T. Holland-Letz$^*$ and H. Naeher
                      and C. Garbe and V. Umansky$^*$ and A. Enk and J. Utikal$^*$
                      and C. Gebhardt$^*$},
      title        = {{D}iminished levels of the soluble form of {RAGE} are
                      related to poor survival in malignant melanoma.},
      journal      = {International journal of cancer},
      volume       = {137},
      number       = {11},
      issn         = {0020-7136},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2017-03756},
      pages        = {2607 - 2617},
      year         = {2015},
      abstract     = {RAGE is a central driver of tumorigenesis by sustaining an
                      inflammatory tumor microenvironment. This study links the
                      soluble forms of RAGE (sRAGE and esRAGE) with clinical
                      outcome of melanoma patients. Moreover, tissue expression of
                      RAGE was analyzed using immunohistochemistry on two
                      independent tissue microarrays (TMA) containing 35 or 257
                      primary melanomas, and 41 or 22 benign nevi, respectively.
                      Serum concentrations of sRAGE and esRAGE were measured in
                      229 Stage III-IV patients using ELISA and plasma
                      concentrations of sRAGE were analyzed in an independent
                      second cohort with 173 samples of Stage I-IV patients. In
                      this cohort, three well-described SNPs in the RAGE gene were
                      analyzed. RAGE protein expression was highly upregulated in
                      primary melanomas compared to benign nevi in the two TMA (p
                      < 0.001 and p = 0.005) as well as in sun-exposed melanomas
                      (p = 0.046). sRAGE and esRAGE were identified as prognostic
                      markers for survival as diminished sRAGE (p = 0.034) and
                      esRAGE (p = 0.012) serum levels correlated with poor overall
                      survival (OS). Multivariate Cox regression analysis showed
                      that diminished serum sRAGE was independently associated
                      with poor survival (p = 0.009). Moreover, diminished sRAGE
                      was strongly associated with impaired OS in the second
                      cohort (p < 0.001). Multivariate Cox regression analysis
                      including the investigated SNPs revealed an independent
                      correlation of the two interacting promoter SNPs with
                      impaired OS. In conclusion, the soluble forms of RAGE and
                      variants in its genetic locus are prognostic markers for
                      survival in melanoma patients with high risk for
                      progression.},
      keywords     = {AGER protein, human (NLM Chemicals) / Advanced
                      Glycosylation End Product-Specific Receptor (NLM Chemicals)
                      / Biomarkers, Tumor (NLM Chemicals)},
      cin          = {G300 / C060},
      ddc          = {610},
      cid          = {I:(DE-He78)G300-20160331 / I:(DE-He78)C060-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:26018980},
      doi          = {10.1002/ijc.29619},
      url          = {https://inrepo02.dkfz.de/record/127733},
}