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Proteomic profiling of N ‐linked glycoproteins identifies C on A ‐binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma
Author(s) -
Qi YiJun,
Ward Douglas G.,
Pang Chun,
Wang QiMing,
Wei Wenbin,
Ma Jin,
Zhang Juan,
Lou Qiang,
Shimwell Neil J.,
Martin Ashley,
Wong Nathalie,
Chao WeiXia,
Wang Ming,
Ma YuanFang,
Johnson Philip J.
Publication year - 2014
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201300226
Subject(s) - hepatocellular carcinoma , microbiology and biotechnology , cathepsin d , chemistry , haptoglobin , glycoprotein , biomarker , blot , western blot , biology , cancer research , biochemistry , enzyme , immunology , gene
The aim of this study was to identify novel biomarkers for the diagnosis of, and potential therapeutic targets for, hepatocellular carcinoma ( HCC ). Multilectin affinity chromatography was used to enrich N‐linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS . Twenty‐eight differentially expressed proteins were identified. Western blotting validated consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin, and higher concentration of procathepsin D (p CD ) in HCC tissues. Knockdown of cathepsin D ( CD ) expression mediated by si RNA significantly inhibited the in vitro invasion of two HCC cell lines, SNU 449 and SNU 473, which normally secrete high‐levels of CD . Prefractionation using individual lectins demonstrated an elevation in C on A ‐binding glycoforms of pro CD and CD in HCC tissues. In the serum of HCC patients, “ C on A ‐binding pro CD ” (ConA‐p CD ) is significantly increased in concentration and this increase is comprised of several distinct upregulated acidic isoforms (p I 4.5–5.5). Receiver operating characteristic analysis showed that the sensitivity and specificity of serum ConA‐p CD for HCC diagnosis were 85% and 80%, respectively. This is the first report that serum ConA‐p CD is increased significantly in HCC and is potentially useful as a serological biomarker for diagnosis of HCC .