Diminished levels of the soluble form of RAGE are related to poor survival in malignant melanoma
Standard
Diminished levels of the soluble form of RAGE are related to poor survival in malignant melanoma. / Wagner, Nikolaus B; Weide, Benjamin; Reith, Maike; Tarnanidis, Kathrin; Kehrel, Coretta; Lichtenberger, Ramtin; Pflugfelder, Annette; Herpel, Esther; Eubel, Jana; Ikenberg, Kristian; Busch, Christian; Holland-Letz, Tim; Naeher, Helmut; Garbe, Claus; Umansky, Viktor; Enk, Alexander; Utikal, Jochen; Gebhardt, Christoffer.
In: INT J CANCER, Vol. 137, No. 11, 01.12.2015, p. 2607-17.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Diminished levels of the soluble form of RAGE are related to poor survival in malignant melanoma
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
N1 - © 2015 UICC.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
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 - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Biomarkers, Tumor
KW - Disease Progression
KW - Female
KW - Humans
KW - Male
KW - Melanoma
KW - Middle Aged
KW - Polymorphism, Single Nucleotide
KW - Prognosis
KW - Promoter Regions, Genetic
KW - Receptor for Advanced Glycation End Products
KW - Up-Regulation
KW - Young Adult
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1002/ijc.29619
DO - 10.1002/ijc.29619
M3 - SCORING: Journal article
C2 - 26018980
VL - 137
SP - 2607
EP - 2617
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
IS - 11
ER -