High GDF-15 Serum Levels Independently Correlate with Poorer Overall Survival of Patients with Tumor-Free Stage III and Unresectable Stage IV Melanoma

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High GDF-15 Serum Levels Independently Correlate with Poorer Overall Survival of Patients with Tumor-Free Stage III and Unresectable Stage IV Melanoma Benjamin Weide, Tina Schäfer, Alexander Martens, Anastasia Kuzkina, Laura Uder, Seema Noor, Claus Garbe, Patrick N. Harter, Michel Mittelbronn, Jörg Wischhusen Journal of Investigative Dermatology Volume 136, Issue 12, Pages 2444-2452 (December 2016) DOI: 10.1016/j.jid.2016.07.016 Copyright © 2016 The Authors Terms and Conditions

Figure 1 Overall survival subsequent to serum sampling of distinct melanoma patient populations according to growth and differentiation factor-15 (GDF-15) serum levels. Kaplan-Meier curves are shown for overall survival subsequent to serum sampling of 468 tumor-free stage III (a), 206 unresectable stage IV (b), and 87 tumor-free stage IV (c) patients with either low (<1.5 ng/ml) or high (≥1.5 ng/ml) GDF-15 levels. Censoring is indicated by vertical lines; P-values were calculated by log-rank statistics. Journal of Investigative Dermatology 2016 136, 2444-2452DOI: (10.1016/j.jid.2016.07.016) Copyright © 2016 The Authors Terms and Conditions

Figure 2 Overall survival subsequent to serum sampling of stage III patients according to combinations of different factors. A nomogram (a) was developed for tumor-free stage III patients using the nomogram function of R considering the relative impact of single independent factors according to multivariate analysis (sGDF-15, sS100B, pattern of locoregional metastasis). A risk score ranging between 0 and 266 points was calculated for 460 stage III patients with complete data. In (b), Kaplan-Meier curves of overall survival subsequent to serum sampling are displayed for different risk score categories. Censoring is indicated by vertical lines. sGDF-15, serum levels of growth and differentiation factor 15; sS100B, S100B in serum. Journal of Investigative Dermatology 2016 136, 2444-2452DOI: (10.1016/j.jid.2016.07.016) Copyright © 2016 The Authors Terms and Conditions

Figure 3 Overall survival subsequent to serum sampling of unresectable stage IV patients according to combinations of different factors. GDF-15 serum levels have an independent impact on overall survival of unresectable stage IV patients in addition to the M category. This is illustrated by the significant differences in OS according to sGDF-15 in both M1a/b patients (a) and M1c patients (b). A nomogram (c) was developed for unresectable stage IV patients using the nomogram function of R considering the relative impact of single independent factors according to multivariate analysis (sGDF-15, sS100B, CNS involvement, and number of involved distant sites). A risk score ranging between 0 and 334 points was calculated for 193 unresectable stage IV patients with complete data. In (d), Kaplan-Meier curves of overall survival subsequent to serum sampling are displayed for different risk score categories. Censoring is indicated by vertical lines. CNS, central nervous system; OS, overall survival; sGDF-15, serum levels of growth and differentiation factor 15; sS100B, S100B in serum. Journal of Investigative Dermatology 2016 136, 2444-2452DOI: (10.1016/j.jid.2016.07.016) Copyright © 2016 The Authors Terms and Conditions