title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: d95442005@ntu.edu.tw.
authors.forename: Wen-Yea
authors.initials: WY
authors.lastname: Yau
authors.forename: Han-Chun
authors.initials: HC
authors.lastname: Shih
authors.forename: Mong-Hsun
authors.initials: MH
authors.lastname: Tsai
authors.forename: Jin-Chuan
authors.initials: JC
authors.lastname: Sheu
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: Lu-Ping
authors.initials: LP
authors.lastname: Chow
mesh_terms: D000974:Antibodies, Antinuclear / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000821:virology; D002460:Cell Line; D000939:Epitopes; D005260:Female; D006509:Hepatitis B / Q000097:blood*; D006515:Hepatitis B virus; D034664:Heterogeneous-Nuclear Ribonucleoprotein L; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000821:virology; D008297:Male
chemical_list: D000974:Antibodies, Antinuclear; D014408:Biomarkers, Tumor; D000939:Epitopes; D034664:Heterogeneous-Nuclear Ribonucleoprotein L
keywords: AFP; Autoantibody; HCC; Hepatitis B virus; Hepatocellular carcinoma; Heterogeneous nuclear ribonucleoprotein L; SERPA; Serological proteome analysis; TAAs; Tumor-associated antigens; hepatocellular carcinoma; heterogeneous nuclear ribonucleoprotein L; hnRNP L; serological proteome analysis.; tumor-associated antigens; α-fetoprotein