Liu Yi, Wang Xiwei, Li Sanglin, Hu Huaidong, Zhang Dazhi, Hu Peng, Yang Yixuan, Ren Hong
Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute for Viral Hepatitis of Chongqing Medical University, Chongqing, China; Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.
J Proteomics. 2014 Jun 25;106:99-112. doi: 10.1016/j.jprot.2014.04.021. Epub 2014 Apr 24.
Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC), the sixth most common cancer worldwide. To explore potential biomarkers for HCC, iTRAQ coupled with mass spectrometry was used to analyze proteins in plasma from individuals with HBV-associated HCC, nonmalignant cirrhosis, chronic hepatitis B, and healthy individuals. Twenty-one aberrantly expressed proteins were identified from HCC patients as compared with nontumor controls. Overexpression of von Willebrand factor (vWF) was confirmed by Western blotting, and immunohistochemical analysis from liver biopsies and ELISA from plasma samples revealed a correlation between vWF expression and HCC clinicopathologic staging. Furthermore, siRNA-induced vWF silencing reduced HBV replication by over two-fold via the interferon-signaling pathway and impaired the invasion and migration of HCC cells in vitro. These results indicate that vWF can serve as a biomarker, and perhaps an alternative target for therapeutic intervention of HCC progression and HBV viral infection.
We report comparative plasma proteome profiles of HBV-associated HCC and nonmalignant chronic liver diseases, including chronic hepatitis B and cirrhosis. The quantification of these datasets showed altered abundance of 21 proteins in HBV-related HCC and provides a reference point for future applied and basic research. In addition, we have demonstrated that the candidate protein vWF is involved in the pathogenesis of HBV infection and replication, and also associated with clinicopathologic staging of HCC patients with HBV infection. Overall these findings provide information on the mechanism of HCC development, which may assist in the development of novel cancer and HBV therapeutic drugs.
慢性乙型肝炎病毒（HBV）感染是肝细胞癌（HCC）的主要危险因素，HCC是全球第六大常见癌症。为了探索HCC的潜在生物标志物，采用iTRAQ结合质谱分析法对HBV相关HCC患者、非恶性肝硬化患者、慢性乙型肝炎患者及健康个体血浆中的蛋白质进行分析。与非肿瘤对照相比，从HCC患者中鉴定出21种异常表达的蛋白质。通过蛋白质印迹法证实了血管性血友病因子（vWF）的过表达，肝活检的免疫组织化学分析和血浆样本的酶联免疫吸附测定显示vWF表达与HCC临床病理分期之间存在相关性。此外，小干扰RNA诱导的vWF沉默通过干扰素信号通路使HBV复制减少两倍以上，并在体外损害HCC细胞的侵袭和迁移。这些结果表明，vWF可作为一种生物标志物，也许还是HCC进展和HBV病毒感染治疗干预的替代靶点。
我们报告了HBV相关HCC与非恶性慢性肝病（包括慢性乙型肝炎和肝硬化）的血浆蛋白质组比较图谱。这些数据集的定量分析显示，HBV相关HCC中有21种蛋白质丰度改变，为未来的应用研究和基础研究提供了参考点。此外，我们已经证明候选蛋白vWF参与HBV感染和复制的发病机制，并且还与HBV感染的HCC患者的临床病理分期相关。总体而言，这些发现提供了有关HCC发生机制的信息，这可能有助于新型癌症和HBV治疗药物的开发。
