Prognostic metabolic markers in cutaneous melanoma

Abstract

Summary Melanoma is the most aggressive skin tumour, being the leading cause of death from skin cancer. Its incidence has increased more rapidly than for any of the top 10 cancers. A low percentage of patients with metastasis (meaning it has spread to other parts of the body) survive over one year after diagnosis, due to the lack of efficient therapy. Not all melanomas are the same, they can vary in how aggressive they are (how quickly they develop and potentially spread) and in their appearance. The authors of this study, from Spain, studied cultured (grown in the lab from a sample) melanoma cells with different aggressiveness features and patients with different types of melanoma lesions. They aimed to find metabolic markers in melanoma that could predict the evolution of the disease. Cellular metabolism is the set of chemical reactions that occur in living organisms in order to maintain life. It is known that the metabolism of cancer cells is different from that of normal cells since they grow and divide rapidly, needing high‐energy supply. In this context, the authors found that proteins (enzymes) related with energy production are altered. These proteins are: the ATP synthase (β‐F1‐ATPase), the heat‐shock protein 60 (HSP60), the glycolytic glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) and the pyruvate kinase M2 (PKM2). These proteins provide the bioenergetic signature (BEC index=β‐F1‐ATPase/HSP60/GAPDH ratio) of cancer. A reduction in BEC index correlates with the aggressiveness of cultured melanoma cells and tumours and worse overall survival in melanoma patients. The authors conclude that the level of metabolic enzymes and BEC status are markers of (indicators of) melanoma stage (how adavanced it is, e.g. if it has spread and by how much) and overall survival in melanoma patients.

A UHPLC-Mass Spectrometry View of Human Melanocytic Cells Uncovers Potential Lipid Biomarkers of Melanoma

“…Metabolic changes are observed in most cancer cells, including accelerated nutrient import and metabolic rewiring to enhanced aerobic glycolysis [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. Alterations in lipid metabolism and the development of a lipogenic phenotype have also emerged as early biochemical hallmarks of cancer cells [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”

“…Alterations in lipid metabolism and the development of a lipogenic phenotype have also emerged as early biochemical hallmarks of cancer cells [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. In this regard, studies assessing the metabolic behavior of melanoma have demonstrated that such phenotypic plasticity confers adaptive advantages favoring proliferation and survival [ 4 , 19 , 20 ]. For instance, while the de novo biosynthesis of fatty acids (FA) is mild in normal adult tissues, the tumorigenesis-associated increase in lipid production enables cells to create a strategically structured new biomass [ 12 , 13 ], helping them better handle changing environmental conditions [ 3 ].…”