Osteoprotegerin as optimal target for the screening of patients with hepatocellular carcinoma at higher risk of mortality

Background-aim Several inflammatory mediators take part in both the start and development of tumour 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 the osteoprotegerin (OPG), member of tumor necrosis factor receptor family, that operate as a decoy receptor for RANKL, avoiding its binding to RANK. It is known that RANKL and RANK expression correlates with metastasis and reduced patient survival but the role of this axis in HCC is not well established. 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. Methods Real-Time PCR experiments as well as OPG plasma and tissue concentrations by immunometric assay were carried out. 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 studied, as well as of OPG plasma and tissue concentrations, was increased as a function of clinical severity, assessed through the MELD score. Significant correlations were found among which between OPG and RANK (r=0.812, pb0.0001), OPG and RANKL (r=0.640, pb0.0023), RANK and RANKL (r=0.885, pb0.0001). A strong correlation was observed between OPG plasma and tissue concentrations (r=0.85, pb0.000). Conclusions Despite additional studies are needed to confirm these findings 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.