TY  - JOUR
AU  - Wagner, Nikolaus B
AU  - Weide, Benjamin
AU  - Reith, Maike
AU  - Tarnanidis, Kathrin
AU  - Kehrel, Coretta
AU  - Lichtenberger, Ramtin
AU  - Pflugfelder, Annette
AU  - Herpel, Esther
AU  - Eubel, Jana
AU  - Ikenberg, Kristian
AU  - Busch, Christian
AU  - Holland-Letz, Tim
AU  - Naeher, Helmut
AU  - Garbe, Claus
AU  - Umansky, Viktor
AU  - Enk, Alexander
AU  - Utikal, Jochen
AU  - Gebhardt, Christoffer
TI  - Diminished levels of the soluble form of RAGE are related to poor survival in malignant melanoma.
JO  - International journal of cancer
VL  - 137
IS  - 11
SN  - 0020-7136
CY  - Bognor Regis
PB  - Wiley-Liss
M1  - DKFZ-2017-03756
SP  - 2607 - 2617
PY  - 2015
AB  - 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.
KW  - AGER protein, human (NLM Chemicals)
KW  - Advanced Glycosylation End Product-Specific Receptor (NLM Chemicals)
KW  - Biomarkers, Tumor (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26018980
DO  - DOI:10.1002/ijc.29619
UR  - https://inrepo02.dkfz.de/record/127733
ER  -