Autoantibody recognition of an N-terminal epitope of hnRNP L marks the risk for developing HBV-related hepatocellular carcinoma.

Abstract

Hepatocellular carcinoma (HCC) is associated with a poor prognosis and remains one of the leading causes of cancer death worldwide. Tumor-associated antigens (TAAs) and autoantibodies have been reported as potential markers in different cancers. Here, we employed an immunoproteomic approach to identify TAAs in the sera of patients with hepatitis B virus-related HCC (HBV-HCC). Immunoreactive spots were excised from 2-DE and analyzed by nano-LC-MS/MS. This analysis identified 16 HCC-associated antigens, including hnRNP L. The antigenicity of hnRNP L was further validated by immunoblotting using recombinant proteins. Autoantibodies against hnRNP L were found in 60% patients with HBV-HCC. Using sera from hnRNP L-positive patients, we found that most of these antibodies recognized glycine-rich region in the N-terminus of hnRNP L. In addition, high titers of autoantibodies against hnRNP L were found in HBV-HCC patients' sera and were associated with increased tumor size and reduced survival rate. hnRNP L protein was also found highly expressed in HCC tissue. Knockdown of hnRNP L significantly suppressed cell growth, migration, and invasion in vitro. Our results indicate that an N-terminal epitope of hnRNP L is a potential biomarker for the diagnosis of HBV-HCC and show that hnRNP L contributes to HCC progression.

BIOLOGICAL SIGNIFICANCE:

In this paper, we employed an immunoproteomic approach to identify TAAs in the sera of patients with hepatitis B virus-related HCC (HBV-HCC). We identified hnRNP L as a tumor-associated antigen in HBV-relative HCC patients. Glycine-rich region located at the N-terminus of hnRNP L constitutes the major epitope. We also demonstrated that hnRNP L is involved in cell proliferation and metastasis.

• Authors: Wen-Yea Yau, Han-Chun Shih, Mong-Hsun Tsai, Jin-Chuan Sheu, Chien-Hung Chen, Lu-Ping Chow
• Journal: Journal of proteomics (J Proteomics) Vol. 94 Pg. 346-58 (Dec 06 2013) ISSN: 1876-7737 [Electronic] Netherlands
• PMID: 24125732 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antibodies, Antinuclear
• Biomarkers, Tumor
• Epitopes
• Heterogeneous-Nuclear Ribonucleoprotein L

Topics

• Antibodies, Antinuclear (blood)
• Biomarkers, Tumor (blood)
• Carcinoma, Hepatocellular (blood, virology)
• Cell Line
• Epitopes
• Female
• Hepatitis B (blood)
• Hepatitis B virus
• Heterogeneous-Nuclear Ribonucleoprotein L
• Humans
• Liver Neoplasms (blood, virology)
• Male