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.
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.


CONCLUSIONS
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.
Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Yi
Y
Liu
Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Xiwei
X
Wang
Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Sanglin
S
Li
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.
Huaidong
H
Hu
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.
Dazhi
D
Zhang
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.
Peng
P
Hu
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. Electronic address: yixuan.yang@hotmail.com.
Yixuan
Y
Yang
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.
Hong
H
Ren
D000328:Adult; D001057:Apolipoproteins E / Q000097:blood; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000821:virology; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D005260:Female; D005634:Fructose-Bisphosphate Aldolase / Q000097:blood; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000097:blood*; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000821:virology; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020543:Proteome; D040901:Proteomics; D034741:RNA, Small Interfering / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism; D015398:Signal Transduction; D014841:von Willebrand Factor / Q000378:metabolism*
D001057:Apolipoproteins E; D015415:Biomarkers; D020543:Proteome; D034741:RNA, Small Interfering; D000685:Serum Amyloid A Protein; D014841:von Willebrand Factor; D005634:Fructose-Bisphosphate Aldolase
Hepatitis B virus; Hepatocellular carcinoma; Isobaric tags for relative and absolute quantitation; von Willebrand factor