CNR Institute of Clinical Physiology, Via Giuseppe Moruzzi 1, 56124, Pisa, Italy.
Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy.
Clin Exp Med. 2021 May;21(2):269-275. doi: 10.1007/s10238-020-00672-x. Epub 2020 Nov 17.
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-α) 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.
Apelin，一种由 77 个氨基酸组成的肽，及其内源性配体血管紧张素样受体 1（APJ），通过增强血管生成、转移、细胞增殖、癌症干细胞的发展和耐药性以及抑制癌细胞凋亡，在肿瘤的发展中发挥关键作用。然而，人们对 Apelin/APJ 系统在肝细胞癌（HCC）中的作用知之甚少。本研究旨在根据肝脏疾病的严重程度（肝受体，LR，n=14，年龄 59.4±1.8）和供体（肝供体，LD，n=14，年龄 62.1±17.3）评估 HCV 阳性 HCC 患者肝移植标本中 Apelin 和 APJ 的表达。通过实时 PCR 分析评估 Apelin/APJ 轴、凋亡和炎症标志物。Apelin/APJ 系统的表达在 LR 中明显高于 LD（p<0.05），特别是在肝脏疾病更严重的患者中。凋亡（Bcl-2、BAX、NOTCH-1、Casp-3）和炎症（IL-6、TNF-α）标志物随着疾病严重程度的增加而增加（p<0.05）。Apelin/APJ 轴与其他标志物之间存在多个显著正相关。尽管需要进一步研究以更好地了解 Apelin/APJ 轴在 HCC 中的作用，但我们的结果表明该轴在 HCC 的发展和进展以及识别新的治疗靶点方面具有潜在作用，为治疗开辟了新途径。
