Assessment of RANKL/RANK/osteoprotegerin system expression in patients with hepatocellular carcinoma.

BACKGROUND: Numerous inflammatory mediators take part in both start and development of tumours and among cytokines family the receptor activator nuclear factor kB-ligand (RANKL) and its receptor RANK seems to have an important role. RANKL is modulated by osteoprotegerin (OPG), member of tumor necrosis factor receptor family, that operate as a decoy receptor for RANKL, avoiding its binding to RANK. RANKL/RANK expression correlates with metastasis and reduced patient survival but the role of this axis in HCC is not well-known. METHODS: Our aim was to study the liver tissues of patients undergoing liver transplantation with HCV-positive HCC (RL, n=10) and of donors (DL, n=14) to assess the RANKL/RANK/OPG system by Real-Time PCR analysis as well as OPG plasma and tissue concentrations by immunometric assay. RESULTS: Significant higher plasma and tissue OPG concentrations in RL compared to DL as well as increased expression of RANKL/RANK/OPG system were observed. The mRNA expression, as well as OPG plasma and tissue concentrations, were increased as a function of clinical severity, assessed through the MELD score. Significant correlations were found. CONCLUSIONS: The results obtained in this study could suggest the RANK/RANKL/OPG pathway as an ideal target for the screening of patients at higher risk of mortality.