title: High GDF-15 Serum Levels Independently Correlate with Poorer Overall Survival of Patients with Tumor-Free Stage III and Unresectable Stage IV Melanoma.
abstract: Biomarkers are strongly needed for diagnostic surveillance of patients with metastatic melanoma. On the basis of its known association with tumor metastasis and its ability to induce cancer cachexia, we investigated serum levels of growth and differentiation factor 15 (sGDF-15) as a marker for overall survival (OS). sGDF-15 was retrospectively measured by ELISA in 761 samples obtained at distinct time points during routine clinical care of patients with stage III/IV melanoma. In the entire cohort, sGDF-15 ≥ 1.5 ng/ml was strongly associated with reduced OS after assessment. Subsequent analyses were performed separately for tumor-free stage III, tumor-free stage IV, and unresectable stage IV patients. For patients with unresectable distant metastasis (n = 206), sGDF-15 was independently associated with OS when considered together with the M-category and superior to serum level of lactate dehydrogenase. Analysis in tumor-free stage III patients during routine surveillance (n = 468) revealed sGDF-15 to be associated with OS and an independent factor when considered together with S100B and the pattern of locoregional metastasis. Only in tumor-free stage IV patients (n = 87) sGDF-15 was not associated with OS. sGDF-15 should thus be further validated as a marker for early detection of recurrence in stage III patients and as a prognostic or predictive marker particularly in the context newly available treatments in unresectable stage IV patients.
authors.affiliation: Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany; Department of Immunology, University of Tübingen, Tübingen, Germany. Electronic address: benjamin.weide@med.uni-tuebingen.de.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Weide
authors.affiliation: Department of Gynecology, University of Würzburg Medical School, Würzburg, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Schäfer
authors.affiliation: Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Martens
authors.affiliation: Department of Gynecology, University of Würzburg Medical School, Würzburg, Germany.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Kuzkina
authors.affiliation: Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Uder
authors.affiliation: Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany.
authors.forename: Seema
authors.initials: S
authors.lastname: Noor
authors.affiliation: Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
authors.affiliation: German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; Edinger Institute (Neurological Institute), Goethe University, Frankfurt/Main, Germany.
authors.forename: Patrick N
authors.initials: PN
authors.lastname: Harter
authors.affiliation: German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; Edinger Institute (Neurological Institute), Goethe University, Frankfurt/Main, Germany.
authors.forename: Michel
authors.initials: M
authors.lastname: Mittelbronn
authors.affiliation: Department of Gynecology, University of Würzburg Medical School, Würzburg, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Wischhusen
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000097:blood*; D016638:Critical Illness / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D018570:Risk Assessment; D012737:Sex Factors; D012878:Skin Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D016019:Survival Analysis; D000096142:Cutaneous Malignant Melanoma
chemical_list: D014408:Biomarkers, Tumor; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15