Type 1 LacNAc and LacdiNAc on N-glycans as potential molecular biomarkers of human melanoma cells

Abstract

Abstract Melanoma is the most dangerous form of skin cancer, as it has a high potential to metastasize. Surgical intervention in the early stages of carcinogenesis is over 90% effective. However, the survival rate is much lower for patients with distant metastases, even with immunomodulatory and targeted therapies. Not all patients respond positively to modern therapies. Therefore, melanoma remains a cancer for which diagnostic and prognostic markers, as well as new therapeutic targets, are necessary. Tumor progression is associated with changes in glycosylation that occur in the early phase of carcinogenesis and evolve as the cancer develops and spreads. Using matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry (MS) and hydrophilic interaction liquid chromatography (HILIC)-high performance liquid chromatography (HPLC), along with exoglycosidase array digestions, we analyzed the N -glycomes of melanocytes and melanoma cells at different stages of cancer development. This study is the first to comprehensively characterize the N -glycome of melanocytes. Unlike melanocytes, melanoma cells express significantly higher levels of type 1 LacNAc units ( P  < 0.001) and triantennary complex-type glycans ( P  < 0.05) than high-mannose-type glycans ( P  < 0.05). All analyzed cell lines possess Lewis X/A epitopes, as well as Galβ1-4Galβ1-4GlcNAc- and Galβ1-3Galβ1-3GlcNAc- units. Conversely, the LacdiNAc motif is unique to melanoma.