Circulating Levels of ADAM-10 and Soluble Standard CD44 in Patients with Hepatocellular Carcinoma: Relationship with Soluble TAM Receptors and their Ligands

Abstract

Objective: The aim of the study was to examine correlations of the plasma levels of soluble (s) CD44 standard (std), and a disintegrin and metalloproteinase (ADAM) 10, with those of the soluble Tyro3, Axl, and Mer receptors (sTAMRs) and their ligands (GAS6 and PROS1) in patients with hepatocellular carcinoma (HCC), and other liver diseases.Method: The subjects were 55 patients with HCC, 4 with fulminant hepatitis (FH), 18 with acute hepatitis (AH), 10 with chronic hepatitis (CH), 20 with liver cirrhosis (LC), and 20 healthy normal controls (NCs). Plasma levels of sCD44std, ADAM10, sTAMRs, GAS6, PROS1, des-γ-carboxy prothrombin (DCP), and des-γ-carboxy GAS6 were measured by enzyme-linked immunosorbent assay.Results: The levels of sCD44std, ADAM10, sTAMRs, and Gas6 were significantly higher in HCC and other liver diseases (except CH) compared to those in NCs, but PROS1 levels in these diseases were significantly lower than those in NCs. These were significant positive correlations of sCD44std levels with ADAM10, and sMer levels in HCC and other liver diseases. SAxl was lower in stage HCC than in stage HCC, but GAS6 increased with progression of HCC stages. There was a significant positive correlation between the levels of DCP and des-γ-carboxy GAS6 in HCC. The subjects were roughly classified into three groups of HCC, inflammatory diseases, and normal controls using ratios of TAMRs and their ligands.Conclusion: The measurement of these blood factors facilitates a unified view of HCC therapy