Serum sphingolipidomic analyses reveal an upregulation of C16- ceramide and sphingosine-1-phosphate in hepatocellular carcinoma
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Georgios Grammatikos1,2, Niklas Schoell2, Nerea Ferreirós3, Dimitra Bon4, Eva Herrmann4, Harald Farnik2, Verena Köberle2, Albrecht Piiper2, Stefan Zeuzem2, Bernd Kronenberger2, Oliver Waidmann2,*, Josef Pfeilschifter1,*
1Goethe University Hospital, Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Frankfurt am Main, Germany
2Goethe University Hospital, Medizinische Klinik 1, Frankfurt am Main, Germany
3Pharmazentrum Frankfurt, Institut für klinische Pharmakologie, Goethe University Hospital, Frankfurt am Main, Germany
4Goethe University, Department of Medicine, Institute of Biostatistics and Mathematical Modelling, Frankfurt am Main, Germany
*These authors contributed equally to this work
Georgios Grammatikos, e-mail: firstname.lastname@example.org
Keywords: S1P, HCC, biomarker, sphingolipid, dihydroceramide
Received: November 17, 2015 Accepted: February 11, 2016 Published: February 26, 2016
We have recently shown that major alterations of serum sphingolipid metabolites in chronic liver disease associate significantly with the stage of liver fibrosis in corresponding patients. In the current study we assessed via mass spectrometry serum concentrations of sphingolipid metabolites in a series of 122 patients with hepatocellular carcinoma (HCC) compared to an age- and sex-matched series of 127 patients with cirrhosis. We observed a highly significant upregulation of long and very long chain ceramides (C16-C24) in the serum of patients with HCC as compared to patients with cirrhosis (P < 0.001). Accordingly, dihydro-ceramides, synthetic precursors of ceramides and notably sphingosine, sphingosine-1-phosphate (S1P) and sphinganine-1-phosphate (SA1P) were upregulated in patients with HCC (P < 0.001). Especially the diagnostic accuracy of C16-ceramide and S1P, assessed by receiver operating curve (ROC) analysis, showed a higher area under the curve (AUC) value as compared to alpha fetoprotein (AFP) (0.999 and 0.985 versus 0.823, P < 0.001 respectively). In conclusion, serum levels of sphingolipid metabolites show a significant upregulation in patients with HCC as compared to patients with cirrhosis. Particularly C16-ceramide and S1P may serve as novel diagnostic markers for the identification of HCC in patients with liver diseases. Our data justify further investigations on the role of sphingolipids in HCC.
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