RT Journal Article T1 Metabolomic profile of cancer stem cell-derived exosomes from patients with malignant melanoma A1 Palacios-Ferrer, José Luis A1 García-Ortega, María Belén A1 Gallardo-Gómez, María A1 García, María Ángel A1 Díaz, Caridad A1 Boulaiz, Houria A1 Valdivia, Javier A1 Jurado, José Miguel A1 Almazan-Fernandez, Francisco M. A1 Arias-Santiago, Salvador A1 Amezcua, Víctor A1 Peinado, Héctor A1 Vicente, Francisca A1 Pérez Del Palacio, José A1 Marchal, Juan A. K1 Biomarkers K1 Cancer stem cells K1 Exosomes K1 Malignant melanoma K1 Metabolomics K1 Biomarcadores K1 Células madre neoplásicas K1 Exosomas K1 Melanoma K1 Metabolómica AB Malignant melanoma (MM) is the most aggressive and life-threatening form of skin cancer. It is characterized by an extraordinary metastasis capacity and chemotherapy resistance, mainly due to melanoma cancer stem cells (CSCs). To date, there are no suitable clinical diagnostic, prognostic or predictive biomarkers for this neoplasia. Therefore, there is an urgent need for new MM biomarkers that enable early diagnosis and effective disease monitoring. Exosomes represent a novel source of biomarkers since they can be easily isolated from different body fluids. In this work, a primary patient-derived MM cell line enriched in CSCs was characterized by assessing the expression of specific markers and their stem-like properties. Exosomes derived from CSCs and serums from patients with MM were characterized, and their metabolomic profile was analysed by high-resolution mass spectrometry (HRMS) following an untargeted approach and applying univariate and multivariate statistical analyses. The aim of this study was to search potential biomarkers for the diagnosis of this disease. Our results showed significant metabolomic differences in exosomes derived from MM CSCs compared with those from differentiated tumour cells and also in serum-derived exosomes from patients with MM compared to those from healthy controls. Interestingly, we identified similarities between structural lipids differentially expressed in CSC-derived exosomes and those derived from patients with MM such as the glycerophosphocholine PC 16:0/0:0. To our knowledge, this is the first metabolomic-based study aimed at characterizing exosomes derived from melanoma CSCs and patients' serum in order to identify potential biomarkers for MM diagnosis. We conclude that metabolomic characterization of CSC-derived exosomes sets an open door to the discovery of clinically useful biomarkers in this neoplasia. PB John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies SN 1574-7891 YR 2020 FD 2020-11-25 LK http://hdl.handle.net/10668/4018 UL http://hdl.handle.net/10668/4018 LA en NO Palacios-Ferrer JL, García-Ortega MB, Gallardo-Gómez M, García MÁ, Díaz C, Boulaiz H, et al. Metabolomic profile of cancer stem cell-derived exosomes from patients with malignant melanoma. Mol Oncol. 2021 Feb;15(2):407-428 DS RISalud RD Apr 14, 2025