| Project Title: | Early detection of HBV-related HCC and identification of HCC metastasis-related biomarkers | |
| Cancer Site: | Liver | |
| Principal Investigator(s): |
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| Participating Institutions: |
Beijing Proteome Research Center (BPRC – Co-Lead Institution)
Beijing Institute of Radiation Medicine (BIRM – Co-Lead Institution) Capital University of Medical Science Cancer Institute Chinese Academy of Medical Sciences Chinese National Center of Biomedical Analysis Fourth Military Medical Univ, Xijing Hospital |
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| Mouse Model(s): | ||
| Technical Approaches: |
Antibody arrays
Cleavable isotope-coded affinity tag (cICAT) ClinProt system (mass spectrometry based biomarker analysis from Bruker Daltonics) Element-coded metal chelate tags High-performance chromatofocusing, high-performance reverse-phase separation Identification of autoantigens by using patient sera to probe 2-D gel separated tumor extract MALDI-TOF/TOF and LC-ESI-MS/MS mass spectrometry Performic oxidation enrichment of sulfonic peptides Protein/peptide quantitation using 16/18O-labeling Stable Isotope Labeling with Amino acids in Cell culture (SILAC) Subtractive immunization to generate monoclonal antibodies (mAb) to poorly immunogenic or rare antigens Transcript arrays Two-dimensional difference gel electrophoresis (DIGE) |
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Annually, hepatocellular carcinoma (HCC) or hepatoma affects more than one million people globally with five-year mortality exceeding 95%. More than half of these cases are in China. With a three-fold increase in incidence in the USA over the past decade, HCC should be viewed as a major health problem for which there is a compelling need for early detection and better treatments. The therapies for treatment of small HCC tumors that offer great hope of controlling this disease have emerged. One of the major impediments to eradicating HCC has been the inability to diagnose these tumors at an early stage. The combination of routine periodic ultrasonography with the measurement of a single tumor marker, alpha-fetoprotein (AFP), has markedly improved early diagnosis. This has prompted a surge in interest in early detection as new tumor markers have been proposed for HCC.
The goal of the HCC Biomarker Discovery Consortium is to 1) identify biomarkers (proteins) that reveal the presence of HBV (hepatitis B virus)-related HCC in a body fluid test and 2) identify HCC metastasis-related biomarkers. A test for early detection would save countless lives, as less than one in five patients with HCC have the fortune to be diagnosed at an early stage, thereby permitting a curative approach to be started. These HCC cancer biomarkers will also be used routinely for population screening, prognosis, monitoring of therapy, and prediction of therapeutic response.
Four main strategies support the Consortium plans, including:
Technology platform - an integrated and high-throughput working platform for investigating the transcriptome (transcript array analysis), proteome (protein expression profile, differential expression profile, PTM profile, and antibodies generation), and metabolome (metabolites profile) including specific strategies for protein pre-fractionation and enrichment prior to mass spectrometric analysis;
HCC biomarker discovery pipeline - a comparative and complementary analysis of HBV-related HCC using human samples including sera/plasma, urine, tumor interstitial fluid, tumor tissue as well as cell lines and animal models; a biomarker discovery pipeline employing immunologic strategies to find biomarkers from tumors as well as the host's own immune response to disease, and thereby identifying two classes of biomarkers that may complement each other in a diagnostic panel;
Antibody-based platform - development of novel analytical techniques such as immunologic assays and monoclonal antibody technology for HCC biomarker discovery;
Bioinformatics platform - application of data standards, data management system, and database systems support for biomarker discovery and validation work.
Yun CAI
Shujun CHENG, M.D.
Jianen GAO
Yuan GAO
Fuchu HE, Ph.D. (Biomarker Team Co-PI) [hefc@nic.bmi.ac.cn;hefc@cnhupo.org]
Ying JIANG
Jianqi LI
Xiaohong QIAN, Ph.D. (Biomarker Team Co-PI)
Qihong SUN, Ph.D. (Biomarker Team Co-PI) [qihongs@vip.sina.com]
Wei SUN
Baocai XING
Jinju YANG
Xiao YANG
Wantao YING
Yangjun ZHANG
Xiaohang ZHAO
Yunping ZHU
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