Proteomic profiling of N ‐linked glycoproteins identifies C on A ‐binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma

• Published in: Proteomics (Weinheim) Vol. 14; no. 2-3; pp. 186 - 195
• Main Authors: Qi, Yi‐Jun, Ward, Douglas G., Pang, Chun, Wang, Qi‐Ming, Wei, Wenbin, Ma, Jin, Zhang, Juan, Lou, Qiang, Shimwell, Neil J., Martin, Ashley, Wong, Nathalie, Chao, Wei‐Xia, Wang, Ming, Ma, Yuan‐Fang, Johnson, Philip J.
• Format: Journal Article
• Language: English
• Published: 01.02.2014
• ISSN: 1615-9853; 1615-9861
• DOI: 10.1002/pmic.201300226

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 .