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000127733 0247_ $$2doi$$a10.1002/ijc.29619
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000127733 1001_ $$0P:(DE-HGF)0$$aWagner, Nikolaus B$$b0$$eFirst author
000127733 245__ $$aDiminished levels of the soluble form of RAGE are related to poor survival in malignant melanoma.
000127733 260__ $$aBognor Regis$$bWiley-Liss$$c2015
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000127733 520__ $$aRAGE is a central driver of tumorigenesis by sustaining an inflammatory tumor microenvironment. This study links the soluble forms of RAGE (sRAGE and esRAGE) with clinical outcome of melanoma patients. Moreover, tissue expression of RAGE was analyzed using immunohistochemistry on two independent tissue microarrays (TMA) containing 35 or 257 primary melanomas, and 41 or 22 benign nevi, respectively. Serum concentrations of sRAGE and esRAGE were measured in 229 Stage III-IV patients using ELISA and plasma concentrations of sRAGE were analyzed in an independent second cohort with 173 samples of Stage I-IV patients. In this cohort, three well-described SNPs in the RAGE gene were analyzed. RAGE protein expression was highly upregulated in primary melanomas compared to benign nevi in the two TMA (p < 0.001 and p = 0.005) as well as in sun-exposed melanomas (p = 0.046). sRAGE and esRAGE were identified as prognostic markers for survival as diminished sRAGE (p = 0.034) and esRAGE (p = 0.012) serum levels correlated with poor overall survival (OS). Multivariate Cox regression analysis showed that diminished serum sRAGE was independently associated with poor survival (p = 0.009). Moreover, diminished sRAGE was strongly associated with impaired OS in the second cohort (p < 0.001). Multivariate Cox regression analysis including the investigated SNPs revealed an independent correlation of the two interacting promoter SNPs with impaired OS. In conclusion, the soluble forms of RAGE and variants in its genetic locus are prognostic markers for survival in melanoma patients with high risk for progression.
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000127733 650_7 $$2NLM Chemicals$$aAGER protein, human
000127733 650_7 $$2NLM Chemicals$$aAdvanced Glycosylation End Product-Specific Receptor
000127733 650_7 $$2NLM Chemicals$$aBiomarkers, Tumor
000127733 7001_ $$aWeide, Benjamin$$b1
000127733 7001_ $$0P:(DE-He78)20246d15b713462495c9cec21a61c7da$$aReith, Maike$$b2$$udkfz
000127733 7001_ $$0P:(DE-He78)0acd2b06b647ba4fff149a3c0eb463bf$$aTarnanidis, Kathrin$$b3$$udkfz
000127733 7001_ $$0P:(DE-HGF)0$$aKehrel, Coretta$$b4
000127733 7001_ $$0P:(DE-HGF)0$$aLichtenberger, Ramtin$$b5
000127733 7001_ $$aPflugfelder, Annette$$b6
000127733 7001_ $$aHerpel, Esther$$b7
000127733 7001_ $$aEubel, Jana$$b8
000127733 7001_ $$aIkenberg, Kristian$$b9
000127733 7001_ $$aBusch, Christian$$b10
000127733 7001_ $$0P:(DE-He78)457c042884c901eb0a02c18bb1d30103$$aHolland-Letz, Tim$$b11$$udkfz
000127733 7001_ $$aNaeher, Helmut$$b12
000127733 7001_ $$aGarbe, Claus$$b13
000127733 7001_ $$0P:(DE-He78)38be34240daf8b47325afc7910e77f7b$$aUmansky, Viktor$$b14$$udkfz
000127733 7001_ $$aEnk, Alexander$$b15
000127733 7001_ $$0P:(DE-He78)a229f7724466e7efadf4a1ace1ff8af3$$aUtikal, Jochen$$b16$$udkfz
000127733 7001_ $$0P:(DE-He78)d239d6a28875058b40c13266babadb58$$aGebhardt, Christoffer$$b17$$eLast author$$udkfz
000127733 773__ $$0PERI:(DE-600)1474822-8$$a10.1002/ijc.29619$$gVol. 137, no. 11, p. 2607 - 2617$$n11$$p2607 - 2617$$tInternational journal of cancer$$v137$$x0020-7136$$y2015
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