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.