Alterations in Plasma Lipid Profiles Associated with Melanoma and Therapy Resistance

• Published in: International journal of molecular sciences Vol. 25; no. 3; p. 1558
• Main Authors: Dei Cas, Michele, Ciniselli, Chiara Maura, Vergani, Elisabetta, Ciusani, Emilio, Aloisi, Mariachiara, Duroni, Valeria, Verderio, Paolo, Ghidoni, Riccardo, Paroni, Rita, Perego, Paola, Beretta, Giovanni Luca, Gatti, Laura, Rodolfo, Monica
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2024
• Subjects: Biomarkers; Cancer; Care and treatment; Ceramides; Cholesterol; Drug resistance; Enzymes; Ethylenediaminetetraacetic acid; Fatty acids; Fatty Acids - metabolism; Gangliosides; Humans; Immunotherapy; Kinases; lipid metabolism; Lipids; Melanoma; Melanoma - drug therapy; Metabolism; Metastasis; Monounsaturated fatty acids; Phosphates; Physiological aspects; Plasma; plasma lipid profiles; Saturated fatty acids; Skin; Skin Neoplasms; Sphingolipids; Sphingosine; Surgery; target therapy; Triglycerides - blood; Vemurafenib; Massachusetts; melanoma; drug resistance; plasma lipid profiles; lipid metabolism; target therapy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25031558

Dysfunctions of lipid metabolism are associated with tumor progression and treatment resistance of cutaneous melanoma. BRAF/MEK inhibitor resistance is linked to alterations of melanoma lipid pathways. We evaluated whether a specific lipid pattern characterizes plasma from melanoma patients and their response to therapy. Plasma samples from patients and controls were analyzed for FASN and DHCR24 levels and lipidomic profiles. FASN and DHCR24 expression resulted in association with disease condition and related to plasma cholesterol and triglycerides in patients at different disease stages ( = 144) as compared to controls ( = 115). Untargeted lipidomics in plasma ( = 40) from advanced disease patients and controls revealed altered levels of different lipids, including fatty acid derivatives and sphingolipids. Targeted lipidomics identified higher levels of dihydroceramides, ceramides, sphingomyelins, ganglioside GM3, sphingosine, sphingosine-1-phosphate, and dihydrosphingosine, saturated and unsaturated fatty acids. When melanoma patients were stratified based on a long/short-term clinical response to kinase inhibitors, differences in plasma levels were shown for saturated fatty acids (FA 16:0, FA18:0) and oleic acid (FA18:1). Our results associated altered levels of selected lipid species in plasma of melanoma patients with a more favorable prognosis. Although obtained in a small cohort, these results pave the way to lipidomic profiling for melanoma patient stratification.