Activity and Expression Pattern of NF-κB/P65 in Peripheral Blood from Hepatocellular Carcinoma Patients - Link to Hypoxia Inducible Factor-1α
Activity and Expression Pattern of NF-κB/P65 in Peripheral Blood from Hepatocellular Carcinoma Patients - Link to Hypoxia Inducible Factor-1α
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DOI：
10.7314/apjcp.2014.15.16.6911
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发表时间：
2014-01-01
影响因子：
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通讯作者：
Ismail, Saber Abdelrahman
中科院分区：
文献类型：
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作者：
Gaballah, Hanaa Hibishy;Zakaria, Soha Said;Ismail, Saber Abdelrahman
背景资料：肝细胞癌是一种复杂的异质性肿瘤，常发生肝内和肝外转移，预后差。HCC发病机制的分子机制仍不清楚。目的：本研究旨在检测肝癌患者外周血单个核细胞中核因子κ B/p65亚单位的丰度和DNA结合活性，并探讨其与缺氧诱导因子1 α（HIF-1 α）的关系及其预后意义。主题和方法：这项研究是在40名患者中进行的，这些患者分为肝硬化（I组）和HCC（II组），此外还有20名健康志愿者（III组）。采用真实的时间PCR检测各组细胞NF-κ B B /P65亚基表达水平，采用转录因子结合免疫分析法检测各组细胞DNA结合活性。血清HIF-1 α水平通过酶联免疫吸附试验（ELISA）进行评估。HCC患者NF-κ B B /P65亚基表达水平、DNA结合活性及血清HIF-1 α水平均显著高于肝硬化组和对照组，且与HCC预后不良指标呈正相关。总之，NF-κ B信号在HCC中被激活，并与疾病预后和高循环水平的HIF-1 α相关。
Background: Hepatocellular carcinoma is a complex and heterogeneous tumor with poor prognosis due to frequent intrahepatic spread and extrahepatic metastasis. The molecular mechanisms underlying HCC pathogenesis still remain obscure. Objectives: We aimed to investigate the abundance and the DNA binding activity of nuclear factor kappa B/p65 subunit in peripheral blood mononuclear cells from patients with HCC and to assess its prognostic significance and association with hypoxia inducible factor one alpha (HIF-1 alpha) in blood. Subjects and methods: This study was carried out on 40 patients classified equally into liver cirrhosis (group I) and HCC (group II), in addition to 20 healthy volunteers (group III). All groups were subjected to measurement of NF-kappa B /P65 subunit expression levels by real time-PCR, and DNA binding activity was evaluated by transcription factor binding immunoassay. Serum HIF-1 alpha levels were estimated by enzyme-linked immunosorbent assay (ELISA). Significant increase of both the expression level and DNA binding activity of NF-kappa B /P65 subunit together with serum HIF-1 alpha levels was noted in HCC patients compared to liver cirrhosis and control subjects, with significant positive correlation with parameters for bad prognosis of HCC. In conclusion, NF-kappa B signaling is activated in HCC and associated with disease prognosis and with high circulating levels of HIF-1 alpha.