Comprehensive characterization of complex glycosphingolipids in human pancreatic cancer tissues

Pancreatic ductal adenocarcinoma (PDAC) is one of the most common causes of cancer-related deaths worldwide, accounting for 90% of primary pancreatic tumors with an average 5-year survival rate of less than 10%. PDAC exhibits aggressive biology, which, together with late detection, results in most PDAC patients presenting with unresectable, locally advanced, or metastatic disease. In-depth lipid profiling and screening of potential biomarkers currently appear to be a promising approach for early detection of PDAC or other cancers. Here, we isolated and characterized complex glycosphingolipids (GSL) from normal and tumor pancreatic tissues of patients with PDAC using a combination of TLC, chemical staining, carbohydrate-recognized ligand-binding assay, and LC/ESI-MS². The major neutral GSL identified were GSL with the terminal blood groups A, B, H, Le^a, Le^b, Le^x, Le^y, P1, and PX2 determinants together with globo- (Gb₃ and Gb₄) and neolacto-series GSL (nLc₄ and nLc₆). We also revealed that the neutral GSL profiles and their relative amounts differ between normal and tumor tissues. Additionally, the normal and tumor pancreatic tissues differ in type 1/2 core chains. Sulfatides and GM₃ gangliosides were the predominant acidic GSL along with the minor sialyl-nLc₄/nLc₆ and sialyl-Le^a/Le^x. The comprehensive analysis of GSL in human PDAC tissues extends the GSL coverage and provides an important platform for further studies of GSL alterations; therefore, it could contribute to the development of new biomarkers and therapeutic approaches.