Is autotaxin (ENPP2) the link between Hepatitis C and hepatocellular cancer?
Is autotaxin (ENPP2) the link between Hepatitis C and hepatocellular cancer?
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DOI：
10.1007/s11605-007-0322-9
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发表时间：
2007-12-01
影响因子：
3.2
通讯作者：
Maluccio, Mary A.
中科院分区：
文献类型：
--
作者：
Cooper, Amanda B.;Wu, Jianmin;Maluccio, Mary A.
前言丙型肝炎是肝细胞癌发生的最重要的危险因素。炎症、纤维化和肝细胞增殖可能通过恶性肝细胞转化或肿瘤微环境中的细胞外基质重塑而导致癌症的发生。本研究的目的是研究丙型肝炎(+/-癌)患者和正常人之间基因表达的差异，以解释癌症风险增加的原因。方法收集3组患者的肝组织：1)健康组，2)非癌丙型肝炎患者，3)丙型肝炎合并肝细胞癌患者。对每组样本进行基因芯片分析。Western印迹和实时聚合酶链式反应(PCR)分析证实了微阵列数据。结果基因芯片分析结果显示，癌症患者与肝炎患者和正常患者相比，其自体趋化蛋白的表达水平明显升高。与溶血磷脂酸信号相关的Rho GTPase结合蛋白(CDC42S)在癌症患者中也过表达。实时定量聚合酶链式反应显示，与正常对照组相比，丙型肝炎(+/-癌)患者体内存在多种自体趋化蛋白相关因子的过度表达。结论丙型肝炎和肝细胞癌患者自体趋化蛋白途径各成分的表达与正常患者存在差异。这值得在早期诊断的背景下进一步研究。
Introduction Hepatitis C is the most significant risk factor for development of hepatocellular carcinoma. Inflammation, fibrosis, and liver cell proliferation may contribute to cancer development either through malignant hepatocyte transformation or extracellular matrix remodeling within the tumor microenvironment. The study objective was to investigate differences in gene expression between patients with Hepatitis C (+/- cancer) and normal that might explain the increased cancer risk.Methods Liver tissue was collected from three patient groups: 1) healthy patients, 2) Hepatitis C patients without cancer, 3) patients with Hepatitis C and hepatocellular carcinoma. Microarray analysis was performed on samples from each group. Western blot and real-time polymerase chain reaction (PCR) analyses corroborated the microarray data. A p value of 0.05 was set as significant.Results Microarray analysis showed overexpression of autotaxin in patients with cancer versus hepatitis patients or normal patients. Rho GTPase binding proteins (Cdc42s) associated with lysophosphatidic acid signaling were also overexpressed in cancer patients. Real-time polymerase chain reaction showed overexpression of several factors associated with autotaxin in patients with Hepatitis C (+/- cancer) versus normal patients.Conclusions Patients with Hepatitis C and hepatocellular carcinoma show differential expression of various components of the autotaxin pathway versus normal patients. This merits further investigation in the context of early diagnosis.