title: Hepatocellular carcinoma protein carbonylation in virus C and metabolic syndrome patients.
abstract: Metabolic syndrome (MS) is becoming the leading cause of chronic liver diseases worldwide. Hepatocellular carcinoma (HCC) development in MS is peculiar compared to other chronic liver diseases. Carbohydrate and lipid metabolic imbalance in MS increase reactive oxygen species damaging proteins. In the present work we study the difference in protein oxidative damage (carbonylation) in human HCC derived from virus C infection (VHC) and from MS (MS_HCC) as the only subjacent cause. We selected a patient cohort containing of 10 non-tumoral and 10 tumoral liver resections in each study group (virus C and MS HCC) based on clinical patient history and histological parameters. Protein samples were labeled to saturation using CF 647-hydrazide™ dye. This approach allows us to perform carbonyl detection alongside with a DIGE experiment. We detected a total of 1184 spots with 36 differentially expressed proteins and 47 spots differentially carbonylated between VHC and MS_HCC (fold change >1.5, p<0.05). VHC up-regulated proteins are involved in signaling pathways related to cancer development such as signaling by EGFR, Wnt, Cdc20 and cell cycle. Further, up-regulated proteins in MS HCC, are implicated in metabolism of carbohydrates and amino acids. Differential carbonylation analysis between VHC and MS_HCC showed protein damage in proteins such as glucose phosphate isomerase, isocitrate dehydrogenase, and 3-ketoacyl-CoA thiolase. Higher protein carbonylation in MS_HCC samples was observed in proteins involved in redox response and lipid metabolism. In conclusion, the observed difference in protein oxidative damage between MS and Virus C derived carcinoma could account for the different cancer development pathway.
authors.affiliation: Institut national de la santé et de la recherche médicale (U1001), Paris, France. Electronic address: fernando-ariel.martin@inserm.fr.
authors.forename: Fernando Ariel
authors.initials: FA
authors.lastname: Martin
authors.affiliation: Hopital Beaujon (Pathology Service), Paris, France.
authors.forename: Mouniya
authors.initials: M
authors.lastname: Mebarki
authors.affiliation: Hopital Beaujon (Pathology Service), Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Paradis
authors.affiliation: Université Pierre et Marie Curie-CNRS UMR 8256, ERL Inserm U1164, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Friguet
authors.affiliation: Institut national de la santé et de la recherche médicale (U1001), Paris, France.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Radman