title: Glycoproteomic discovery of serological biomarker candidates for HCV/HBV infection-associated liver fibrosis and hepatocellular carcinoma.
abstract: We previously proposed a high-throughput strategy to discover serological biomarker candidates of cancer. This strategy focuses on a series of candidate glycoproteins that are specifically expressed in the original tissues (cells) of the target cancer and that carry glycan structures associated with carcinogenesis [Narimatsu, H., et al. FEBS J.2010, 277(1), 95-105]. Here, we examined the effectiveness of our strategy in identifying biomarkers to assess progression of liver fibrosis and for the early detection of hepatocellular carcinoma (HCC). On the basis of the results of lectin array analyses in culture media of hepatoma cell lines, we captured glycopeptides carrying AAL-ligands (fucosylated glycans) or DSA-ligands (branched glycans) from digests of culture media proteins and sera from HCC patients with a background of liver cirrhosis (LC). Glycoproteins were identified by the IGOT-LC-MS method. In all, 21 candidates were selected from 744 AAL-bound glycoproteins for further verification according to (i) their abundance in serum, (ii) their specific expression in liver, and (iii) the availability of antibodies to the glycoproteins. All selected candidates showed enhancement of AAL-reactivity in sera of HCC patients compared with that of healthy volunteers (HV). These results indicate that our glycoproteomic strategy is effective for identifying multiple glyco-biomarker candidates in a high-throughput manner.
authors.affiliation: Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kaji
authors.forename: Makoto
authors.initials: M
authors.lastname: Ocho
authors.forename: Akira
authors.initials: A
authors.lastname: Togayachi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kuno
authors.forename: Maki
authors.initials: M
authors.lastname: Sogabe
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohkura
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nozaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Angata
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Chiba
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ozaki
authors.forename: Jun
authors.initials: J
authors.lastname: Hirabayashi
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizokami
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Ikehara
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narimatsu
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000209:etiology / Q000821:virology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002846:Chromatography, Affinity; D006020:Glycopeptides / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000150:complications / Q000821:virology; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications / Q000821:virology; D006801:Humans; D037102:Lectins / Q000737:chemistry; D008103:Liver Cirrhosis / Q000097:blood* / Q000209:etiology / Q000821:virology; D008113:Liver Neoplasms / Q000097:blood* / Q000209:etiology / Q000821:virology; D008875:Middle Aged; D011134:Polysaccharides / Q000097:blood*
chemical_list: D015415:Biomarkers; D006020:Glycopeptides; D037102:Lectins; D011134:Polysaccharides