Prognostic value of cell sphingolipid profile and plasma membrane sialidase Neu3 expression in melanoma

Melanoma is the most aggressive and lethal form of skin cancer. Annually, it is responsible for at least 48,000 deaths worldwide and its incidence has risen sharply in recent decades. In addition to characteristic genetic lesions, melanoma cells display a characteristic repertoire of sphingolipids, especially gangliosides, very different from healthy melanocytes. In this report, we analysed the sphingolipid pattern and the mRNA expression of enzymes involved in sphingolipid metabolism in a large panel of short-term melanoma cell lines established from surgical specimens, isolated from VGP (vertical growth phase) primary tumours and from metastatic lesions of melanoma patients. We demonstrated that the gangliosides profile of melanoma cells varied from patient to patient and that an interesting correlation between ganglioside pattern and patients’ survival existed. In particular, the shortest survival time was recorded in patients carrying tumour cells marked by the presence of GM3, GD3, and sialylparagloboside (Hazard ratio: 7.2, according to Kaplain Meyer survival analysis). Sialylparagloboside is known to be the synthetic precursor of Sialyl Lewis X epitope that is related with increased metastatic potential of cancer cells. In addition, also the expression of some key enzymes involved in gangliosides synthesis and catabolism correlated with patients’ survival. In particular, the expression of the plasma membrane sialidase NEU3 was increased in many melanoma cell lines established from patients, as compared to expression detected in normal melanocytes. This increment was inversely correlated to patients’ survival (Hazard ratio: 3, according to Kaplain Meyer survival analysis). These results suggest the employment of gangliosides pattern and of NEU3 expression as markers to classify melanomas in addition to histopathologic criteria. 1. Furukawa K et al Proteomics 2008;8(16): 3312-6.