Science China Life Sciences

, Volume 56, Issue 7, pp 638–646

Secretory/releasing proteome-based identification of plasma biomarkers in HBV-associated hepatocellular carcinoma

  • Lei Yang
  • WeiQi Rong
  • Ting Xiao
  • Ying Zhang
  • Bin Xu
  • Yu Liu
  • LiMing Wang
  • Fan Wu
  • Jun Qi
  • XiuYing Zhao
  • HongXia Wang
  • NaiJun Han
  • SuPing Guo
  • JianXiong Wu
  • YanNing Gao
  • ShuJun Cheng
Open Access
Research Paper

DOI: 10.1007/s11427-013-4497-x

Cite this article as:
Yang, L., Rong, W., Xiao, T. et al. Sci. China Life Sci. (2013) 56: 638. doi:10.1007/s11427-013-4497-x

Abstract

For successful therapy, hepatocellular carcinoma (HCC) must be detected at an early stage. Herein, we used a proteomic approach to analyze the secretory/releasing proteome of HCC tissues to identify plasma biomarkers. Serum-free conditioned media (CM) were collected from primary cultures of cancerous tissues and surrounding noncancerous tissues. Proteomic analysis of the CM proteins permitted the identification of 1365 proteins. The enriched molecular functions and biological processes of the CM proteins, such as hydrolase activity and catabolic processes, were consistent with the liver being the most important metabolic organ. Moreover, 19% of the proteins were characterized as extracellular or membrane-bound. For validation, secretory proteins involved in transforming growth factor-β signaling pathways were validated in plasma samples. Alphafetoprotein (AFP), metalloproteinase (MMP)1, osteopontin (OPN), and pregnancy-specific beta-1-glycoprotein (PSG)9 were significantly increased in HCC patients. The overall performance of MMP1 and OPN in the diagnosis of HCC remained greater than that of AFP. In addition, this study represents the first report of MMP1 as a biomarker with a higher sensitivity and specificity than AFP. Thus, this study provides a valuable resource of the HCC secretome with the potential to investigate serological biomarkers. MMP1 and OPN could be used as novel biomarkers for the early detection of HCC and to improve the sensitivity of biomarkers compared with AFP.

Keywords

hepatocellular carcinoma (HCC) secretome biomarker MMP1 OPN PSG9 
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Supplementary material

11427_2013_4497_MOESM1_ESM.pdf (431 kb)
Supplementary material, approximately 430 KB.
11427_2013_4497_MOESM2_ESM.xls (672 kb)
Supplementary material, approximately 671 KB.

Copyright information

© The Author(s) 2013

Authors and Affiliations

  • Lei Yang
    • 1
  • WeiQi Rong
    • 2
  • Ting Xiao
    • 1
  • Ying Zhang
    • 1
  • Bin Xu
    • 3
  • Yu Liu
    • 1
  • LiMing Wang
    • 2
  • Fan Wu
    • 2
  • Jun Qi
    • 4
  • XiuYing Zhao
    • 5
  • HongXia Wang
    • 3
  • NaiJun Han
    • 1
  • SuPing Guo
    • 1
  • JianXiong Wu
    • 2
  • YanNing Gao
    • 1
  • ShuJun Cheng
    • 1
  1. 1.State Key Laboratory of Molecular Oncology, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, Cancer Institute (Hospital)Peking Union Medical College & Chinese Academy of Medical SciencesBeijingChina
  2. 2.Department of Abdominal Surgery, Cancer Institute (Hospital)Peking Union Medical College & Chinese Academy of Medical SciencesBeijingChina
  3. 3.National Center of Biomedical AnalysisBeijingChina
  4. 4.Clinical Laboratory, Cancer Institute (Hospital)Peking Union Medical College & Chinese Academy of Medical SciencesBeijingChina
  5. 5.Clinical Laboratory, Beijing You’an HospitalCapital Medical UniversityBeijingChina

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