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Altered Sphingolipid Metabolism in Patients with Metastatic Pancreatic Cancer
Pennsylvania state Hershey cancer institute, Hershey, PA17033, USA
Department of pharmacology, Hershey, PA17033, USA
Department of gastrointestinal medical oncology, the University of Texas MD Anderson cancer center, Houston, TX77030, USA
Department of orthopedics Pennsylvania state college of medicine, 500 University Drive, Hershey, PA 17033, USA
* Author to whom correspondence should be addressed.
Received: 23 May 2013; in revised form: 10 July 2013 / Accepted: 24 July 2013 / Published: 25 July 2013
Abstract: 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.
Keywords: sphingolipids; pancreatic cancer; ceramide; lipidomics; CXCL10
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MDPI and ACS Style
Jiang, Y.; DiVittore, N.A.; Young, M.M.; Jia, Z.; Xie, K.; Ritty, T.M.; Kester, M.; Fox, T.E. Altered Sphingolipid Metabolism in Patients with Metastatic Pancreatic Cancer. Biomolecules 2013, 3, 435-448.
Jiang Y, DiVittore NA, Young MM, Jia Z, Xie K, Ritty TM, Kester M, Fox TE. Altered Sphingolipid Metabolism in Patients with Metastatic Pancreatic Cancer. Biomolecules. 2013; 3(3):435-448.
Jiang, Yixing; DiVittore, Nicole A.; Young, Megan M.; Jia, Zhiliang; Xie, Keping; Ritty, Timothy M.; Kester, Mark; Fox, Todd E. 2013. "Altered Sphingolipid Metabolism in Patients with Metastatic Pancreatic Cancer." Biomolecules 3, no. 3: 435-448.