Although numerous genetic mutations and amplifications have been identified in
pancreatic cancer, much of the molecular pathogenesis of the disease remains undefined. While proteomic and transcriptomic analyses have been utilized to probe and characterize pancreatic
tumors, lipidomic analyses have not been applied to identify perturbations in
pancreatic cancer patient samples. Thus, we utilized a mass spectrometry-based lipidomic approach, focused towards the
sphingolipid class of
lipids, to quantify changes in human
pancreatic cancer tumor and plasma specimens. Subgroup analysis revealed that patients with positive
lymph node metastasis have a markedly higher level of
ceramide species (C16:0 and C24:1) in their
tumor specimens compared to
pancreatic cancer patients without nodal disease or to patients with
pancreatitis. Also of interest,
ceramide metabolites, including phosphorylated (sphingosine- and sphinganine-1-phosphate) and glycosylated (cerebroside) species were elevated in the plasma, but not the pancreas, of
pancreatic cancer patients with nodal disease. Analysis of plasma level of
cytokine and
growth factors revealed that
IL-6,
IL-8, CCL11 (eotaxin),
EGF and IP10 (
interferon inducible protein 10, CXCL10) were elevated in patients with positive lymph nodes
metastasis, but that only IP10 and
EGF directly correlated with several
sphingolipid changes. Taken together, these data indicate that
sphingolipid metabolism is altered in human
pancreatic cancer and associated with advanced disease. Assessing plasma and/or tissue
sphingolipids could potentially risk stratify patients in the clinical setting.