The role of von Willebrand factor as a biomarker of tumor development in hepatitis B virus-associated human hepatocellular carcinoma: A quantitative proteomic based study

• Published in: Journal of proteomics Vol. 106; pp. 99 - 112
• Main Authors: Liu, Yi, Wang, Xiwei, Li, Sanglin, Hu, Huaidong, Zhang, Dazhi, Hu, Peng, Yang, Yixuan, Ren, Hong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 25.06.2014
• Subjects: Adult; Apolipoproteins E - blood; Biomarkers - blood; Carcinoma, Hepatocellular - blood; Carcinoma, Hepatocellular - virology; Cell Line, Tumor; Cell Movement; Disease Progression; Female; Fructose-Bisphosphate Aldolase - blood; Gene Expression Regulation, Neoplastic; Gene Silencing; Hepatitis B virus; Hepatitis B, Chronic - blood; Hepatocellular carcinoma; Humans; Isobaric tags for relative and absolute quantitation; Liver Neoplasms - blood; Liver Neoplasms - virology; Male; Mass Spectrometry; Middle Aged; Neoplasm Invasiveness; Proteome; Proteomics; RNA, Small Interfering - metabolism; Serum Amyloid A Protein - metabolism; Signal Transduction; von Willebrand factor; von Willebrand Factor - metabolism; iTRAQ; Hepatocellular carcinoma; Hepatitis B virus; MS/MS; von Willebrand factor; Isobaric tags for relative and absolute quantitation
• ISSN: 1874-3919; 1876-7737
• DOI: 10.1016/j.jprot.2014.04.021

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. [Display omitted] •Twenty-one aberrantly expressed proteins are identified in the plasma of HCC patients.•Overexpression of vWF, SAA, APOE, and ALDOB in HCC is confirmed with WB and IHC.•Knockdown of vWF impairs HCC cell migration and invasion in vitro.•vWF silencing suppresses STAT3, pY705-STAT3, MMP2 and MMP9 protein expression.•vWF depletion reduces HBV replication via the interferon-signaling pathway.