Journal Article

DKFZ-2017-03756

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Diminished levels of the soluble form of RAGE are related to poor survival in malignant melanoma.

Wagner, N. B. (First author)DKFZ* ; Weide, B. ; Reith, M.DKFZ* ; Tarnanidis, K.DKFZ* ; Kehrel, C.DKFZ* ; Lichtenberger, R.DKFZ* ; Pflugfelder, A. ; Herpel, E. ; Eubel, J. ; Ikenberg, K. ; Busch, C. ; Holland-Letz, T.DKFZ* ; Naeher, H. ; Garbe, C. ; Umansky, V.DKFZ* ; Enk, A. ; Utikal, J.DKFZ* ; Gebhardt, C. (Last author)DKFZ*

2015
Wiley-Liss Bognor Regis

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Please use a persistent id in citations: doi:10.1002/ijc.29619

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.

Keyword(s): AGER protein, human ; Advanced Glycosylation End Product-Specific Receptor ; Biomarkers, Tumor

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Contributing Institute(s):

1. KKE Dermatoonkologie (G300)
2. Biostatistik (C060)

Research Program(s):

1. 317 - Translational cancer research (POF3-317) (POF3-317)

Appears in the scientific report 2015

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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