The serum metabolome serves as a diagnostic biomarker and discriminates patients with melanoma from healthy individuals.

Melanoma is a deadly cancer with increasing incidence and mortality rates, and biomarkers for diagnosis are urgently needed. The impact of the microbiome, genetic factors, and immunologic markers on disease outcomes is described, but a comprehensive serum metabolome profiling is missing. The serum metabolome of patients with melanoma might be valuable to identify potential biomarkers. We present an untargeted metabolomics analysis in an exploratory cohort (87 patients with melanoma), an independent validation cohort (37 additional patients with melanoma featuring late-stage tumors), and 18 healthy control individuals, revealing striking differences. We identify and validate six serum metabolites that can predict the diagnosis of melanoma with an area under the curve (AUC) >0.9544 in advanced-stage melanoma. The AUC of our lead biomarker, muramic acid, is 0.964, 0.908, and 0.9936 in patients with stage I (n = 22), stage II (n = 67), and advanced melanoma (n = 86), respectively. In summary, we identify potentially very powerful diagnostic biomarkers for clinical practice.