title: Serum anti-Ku86 is a potential biomarker for early detection of hepatitis C virus-related hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is one of the most common cancers worldwide and the third most common cause of cancer-related death. Imaging studies including ultrasound and computed tomography are recommended for early detection of HCC, but they are operator dependent, costly and involve radiation. Therefore, there is a need for simple and sensitive serum markers for the early detection of hepatocellular carcinoma (HCC). In our recent proteomic studies, a number of proteins overexpressed in HCC tissues were identified. We thought if the serum autoantibodies to these overexpressed proteins were detectable in HCC patients. Of these proteins, we focused on Ku86, a nuclear protein involved in multiple biological processes and aimed to assess the diagnostic value of serum anti-Ku86 in the early detection of HCC. Serum samples were obtained prior to treatment from 58 consecutive patients with early or relatively early hepatitis C virus (HCV)-related HCC and 137 patients with HCV-related liver cirrhosis without evidence of HCC. Enzyme immunoassays were used to measure serum levels of autoantibodies. Serum levels of anti-Ku86 antibodies were significantly elevated in HCC patients compared to those in liver cirrhosis patients (0.41±0.28 vs. 0.18±0.08Abs at 450nm, P<0001). Setting the cut-off level to give 90% specificity, anti-Ku86 was positive in 60.7% of stage I solitary tumor <2cm in diameter, whereas the sensitivities of alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II) were 17.8% and 21.4%, respectively. The results of ROC analyses indicated the better performance of anti-Ku86 for early detection of HCC. Serum anti-Ku86 levels decreased after surgical resection of the tumors in the 12 HCC cases tested, Elevation of anti-Ku86 in solid tumors other than liver was minimal. Serum anti-Ku86 is a potential biomarker for early detection of HCV-related HCC. Further studies in a larger number of HCC patients with various etiologies are needed to further evaluate the diagnostic and pathophysiological roles of elevation of serum anti-Ku86 in early HCC.
authors.affiliation: Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University and Divisions of Laboratory Medicine, Clinical Genetics and Proteomics, Chiba University Hospital, Chiba, Japan. fnomura@faculty.chiba-u.jp
authors.forename: Fumio
authors.initials: F
authors.lastname: Nomura
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sogawa
authors.forename: Kenta
authors.initials: K
authors.lastname: Noda
authors.forename: Masanori
authors.initials: M
authors.lastname: Seimiya
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Matsushita
authors.forename: Toshihide
authors.initials: T
authors.lastname: Miura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tomonaga
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yoshitomi
authors.forename: Fumio
authors.initials: F
authors.lastname: Imazeki
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Takizawa
authors.forename: Kaoru
authors.initials: K
authors.lastname: Mogushi
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
mesh_terms: D000368:Aged; D034961:Antigens, Nuclear / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D014408:Biomarkers, Tumor / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis* / Q000821:virology; D004268:DNA-Binding Proteins / Q000276:immunology*; D005260:Female; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D000072200:Ku Autoantigen; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000821:virology; D008297:Male; D008875:Middle Aged
chemical_list: D034961:Antigens, Nuclear; D001323:Autoantibodies; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen