title: Quantitative Proteomics Analysis of Tissue Interstitial Fluid for Identification of Novel Serum Candidate Diagnostic Marker for Hepatocellular Carcinoma.
abstract: Hepatocellular carcinoma (HCC) is the fifth most common malignant cancer in the world. The sensitivity of alpha-fetoprotein (AFP) is still inadequate for HCC diagnosis. Tissue interstitial fluid (TIF), as the liquid microenvironment of cancer cells, was used for biomarker discovery in this study. Paired tumor and nontumor TIF samples from 6 HBV-HCC patients were analyzed by a proteomic technique named iTRAQ (isobaric tag for relative and absolute quantitation). Totally, 241 up-regulated proteins (ratio ≥ 1.3, p < 0.05) and 288 down-regulated proteins (ratio ≤ -1.3, p < 0.05) in tumor TIF were identified. Interestingly, proteins in S100 family were found remarkably up-regulated in tumor TIF. One dramatically up-regulated protein S100A9 (ratio = 19) was further validated by ELISA in sera from liver cirrhosis (LC, HCC high risk population) and HCC patients (n = 47 for each group). The level of this protein was significantly elevated in HCC sera compared with LC (p < 0.0001). The area under the curve of this protein to distinguish HCC from LC was 0.83, with sensitivity of 91% (higher than AFP) and specificity of 66%. This result demonstrated the potential of S100A9 as a candidate HCC diagnostic biomarker. And TIF was a kind of promising material to identify candidate tumor biomarkers that could be detected in serum.
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Beijing Institute of Radiation Medicine, Beijing 102206, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Beijing Cancer Hospital, Beijing 100036, China.
authors.forename: Baocai
authors.initials: B
authors.lastname: Xing
authors.affiliation: AB SCIEX, Beijing 100015, China.
authors.forename: Lihai
authors.initials: L
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Beijing Institute of Radiation Medicine, Beijing 102206, China.|MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Zhilei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: 302 Hospital of PLA, Beijing 100039, China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Mu
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Beijing Institute of Radiation Medicine, Beijing 102206, China.
authors.forename: Longqin
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Beijing Institute of Radiation Medicine, Beijing 102206, China.
authors.forename: Handong
authors.initials: H
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute &Hospital, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing 100021, China.
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Beijing Institute of Radiation Medicine, Beijing 102206, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Qian
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Beijing Institute of Radiation Medicine, Beijing 102206, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Beijing Institute of Radiation Medicine, Beijing 102206, China.|Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood; D040502:Calgranulin B / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis*; D045604:Extracellular Fluid / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D040901:Proteomics / Q000379:methods*; D012680:Sensitivity and Specificity; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D040502:Calgranulin B