Glycoproteomic Discovery of Serological Biomarker Candidates for HCV/HBV Infection-Associated Liver Fibrosis and Hepatocellular Carcinoma
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- 作者：Hiroyuki Kaji ; Makoto Ocho ; Akira Togayachi ; Atsushi Kuno ; Maki Sogabe ; Takashi Ohkura ; Hirofumi Nozaki ; Takashi Angata ; Yasunori Chiba ; Hidenori Ozaki ; Jun Hirabayashi ; Yasuhito Tanaka ; Masashi Mizokami ; Yuzuru Ikehara ; Hisashi Narimatsu
- 刊名：Journal of Proteome Research
- 出版年：2013
- 出版时间：June 7, 2013
- 年：2013
- 卷：12
- 期：6
- 页码：2630-2640
- 全文大小：410K
- 年卷期：v.12,no.6(June 7, 2013)
- ISSN：1535-3907
文摘
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鈥?05]. 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鈥揗S 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.