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Plasma proteasome level is a reliable early marker of malignant transformation of liver cirrhosis
  1. Laurent Henry (laurent.henry{at}univ-montp1.fr)
  1. Université Montpellier I, UFR Médecine, Nîmes, France
    1. Thierry Lavabre-Bertrand (tlavabre{at}univ-montp1.fr)
    1. Université Montpellier I, UFR Médecine, et CHU Nîmes, France
      1. Lucile Vercambre (l-vercambre{at}chu-montpellier.fr)
      1. Service des Maladies de l'Appareil Digestif, Centre Hospitalier Universitaire, Montpellier, France
        1. Jeanne Ramos (j-ramos{at}chu-montpellier.fr)
        1. Laboratoire d’Anatomie Pathologique, Centre Hospitalier Universitaire, Montpellier, France
          1. Serge Carillo (serge.carillo{at}univ-montp1.fr)
          1. Université Montpellier I, UFR Médecine, et CHU Nîmes, France
            1. Isabelle Guiraud (isabelle.guiraud{at}univ-montp1.fr)
            1. Université Montpellier I, UFR Médecine, Nîmes, France
              1. Philippe Pouderoux (philippe.pouderoux{at}chu-nimes.fr)
              1. HOPITAL CAREMEAU, France
                1. Mickael Bismuth (m-bismuth{at}chu-montpellier.fr)
                1. Service des Maladies de l'Appareil Digestif, Centre Hospitalier Universitaire, Montpellier, France
                  1. Christophe Demattei (christophe.demattei{at}chu-nimes.fr)
                  1. Département d'Information Médicale, CHU Nimes, France
                    1. Yohan Duny (yohan.duny{at}inserm.fr)
                    1. Département d'Information Médicale, CHU Nimes, France
                      1. Iphigénie Chaze (iphigeniechaze{at}hotmail.com)
                      1. Service des Maladies de l'Appareil Digestif, Centre Hospitalier Universitaire, Montpellier, France
                        1. Natalie Funakoshi (natfun{at}aliceadsl.fr)
                        1. Université Service des Maladies de l'Appareil Digestif, Centre Hospitalier Universitaire, Montpellie, France
                          1. Jean Paul Bureau (jean-paul.bureau{at}univ-montp1.fr)
                          1. Université Montpellier I, UFR Médecine, Nîmes, France
                            1. Jean-Pierre Daures (jean.pierre.daures{at}chu-nimes.fr)
                            1. Département d'Information Médicale, CHU Nimes, France
                              1. Pierre Blanc (p-blanc{at}chu-montpellier.fr)
                              1. Service des Maladies de l'Appareil Digestif, Centre Hospitalier Universitaire, Montpellier, France

                                Abstract

                                Proteasomes are the main non-lysosomal proteolytic structures which regulate crucial cellular processes. Circulating proteasome levels can be measured using an ELISA test and can be considered as a tumor marker in several types of malignancy.

                                Given that there is no sensitive marker of hepatocellular carcinoma (HCC) in cirrhotic patients, we measured plasma proteasome levels in 83 cirrhotic patients (33 without HCC, 50 with HCC) and 40 controls. HCC patients were sub-classified in 3 groups according to tumor mass. Alpha-fetoprotein (AFP) was also measured.

                                Plasma proteasome levels were significantly higher in HCC patients compared to controls (4841 ± 613 ng/mL vs 2534 ± 187 ng/mL; p < 0.001) and compared to cirrhotic patients without HCC (2077 ± 112 ng/mL; p = < 0.001). This difference remained significant when the subgroup of patients with low tumor mass (proteasome level 3970 ± 310 ng/mL, p < 0.001) was compared to controls and cirrhotic patients without HCC. Plasma proteasome levels were independent of the cause of cirrhosis and were weakly correlated with AFP levels. With a cut-off of 2900 ng/mL, diagnostic specificity for HCC was 97% with a sensitivity of 72%, better than results obtained with AFP. Diagnostic relevance of plasma proteasome measurement was also effective in low tumor mass patients (sensitivity 76.2% versus 57.1% for AFP).

                                In conclusion, the plasma proteasome level is a reliable marker of malignant transformation in cirrhotic patients, even in the event of low tumor mass.

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