Comparative Analysis of Metabolic Signature from Malignant Melanoma and Uninvolved Skin.

e20016 Background: In a variety of malignancies, metabolites have been investigated in order to identify potential biomarkers and therapeutic targets. Current clinical strategy for staging and prognostication of malignant melanoma relies mainly upon the AJCC classification. However, this clinicopathological stage gives little insight into the biological characteristics of the tumor. We hypothesized that global metabolic profiling of malignant melanoma would define metabolic signatures that discriminate malignant from normal skin and may also distinguish clinicopathological and prognostical features. In this study we compared metabolic signatures from either primary melanoma or melanoma metastases with matched control non-neoplastic skin from the same patient. Methods: Human fresh (non-fixed) biopsied melanoma samples and matched controls from uninvolved skin were obtained from 40 melanoma patients (primary melanomas: n = 23, cutaneous melanoma metastases: n = 17) during surgery and subjected to a two-stage metabolomic screening experiment using gas chromatography/mass spectrometry (GC/MS). Results: In a set of 300 chemically defined metabolites, the metabolic profiles of primary melanoma and metastatic tissue suggested a key role for metabolic pathways of apoptosis, energy metabolism, and proliferation. Several metabolites including cyclopentenone, methylsalicylate, malonate, trimethyl-cis-aconitate, and dimethyluracil differed significantly between melanoma and normal tissue meeting the discovery (p < 2.0×10(-4)) and the replication thresholds (p < 3.5×10(-3)). Cyclopentenone prostaglandins have been shown to have a proapoptotoc effect on melanoma cells and to activate the nuclear factor E2-related factor 2 (Nrf2)- pathway, which, in turn, contributes to tumorigenesis via protection from tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis. Conclusions: Our results illustrate the potential of GC/MS to specify the metabolic signature of melanoma. We found clear differences between primary melanoma, metastatic tissue and uninvolved skin. Metabolomics may help to characterize novel pathways and potential new biomarkers in melanoma.