Evaluation of Apelin/APJ system expression in hepatocellular carcinoma as a function of clinical severity

Apelin, a peptide of 77 amino acids, and its endogenous ligand, angiotensin-like-receptor 1 (APJ), play a key role in the development of tumors by enhancing angiogenesis, metastasis, cell proliferation, development of cancer stem cells and drug resistance and inhibiting apoptosis of cancer cells. However, little is known about Apelin/APJ system involvement in hepatocellular carcinoma (HCC). The aim of this study was to evaluate Apelin and APJ expression in liver specimens, obtained from subjects with HCV-positive HCC who underwent liver transplantation, according to liver disease severity (liver recipients, LR, n = 14, age 59.4 +/- 1.8) and in donors (liver donors, LD, n = 14, age 62.1 +/- 17.3). Apelin/APJ axis, apoptotic and inflammatory markers were evaluated by Real-Time PCR analysis. The Apelin/APJ system expression resulted significantly higher in LR in comparison with LD (p < 0.05), in particular in those with more severe liver disease. The apoptotic (Bcl-2, BAX, NOTCH-1, Casp-3) and inflammatory (IL-6, TNF-alpha) markers were increased as a function of disease severity (p < 0.05). Multiple significant positive correlations were found between Apelin/APJ axis and the other markers. Although further investigations are needed to better understand the role of Apelin/APJ axis in HCC, our result indicated a potential role of this axis in its development and progression as well as in recognizing novel therapeutic targets opening a new avenue for treatment.