title: Human plasma carboxylesterase 1, a novel serologic biomarker candidate for hepatocellular carcinoma.
abstract: To identify and characterize a serologic glycoprotein biomarker for hepatocellular carcinoma (HCC), multi-lectin affinity chromatography was used to isolate intracellular N-linked glycoprotein fractions from five paired non-tumor and tumor tissues. From the series of 2-D DIGE targeted differentially expressed N-linked glycoproteins, we identified human liver carboxylesterase 1 (hCE1), which was remarkably down-regulated in tumor tissues, a finding confirmed by Western blot, a quantitative real-time RT-PCR, and immunohistochemical staining of non-tumor and tumor tissues from total 58 HCC patients. To investigate whether hCE1 is also present in human plasma, we employed a magnetic bead-based immunoprecipitation followed by nano-LC-MS/MS analysis, and we found for the first time that hCE1 is present in human plasma as opposed to that in liver tissues. That is, from normalization of hCE1 signal by the immunoprecipitation and Western blot analysis, hCE1 levels were increased in plasma specimens from HCC patients than in plasma from other disease patient groups (e.g. liver cirrhosis, chronic hepatitis, cholangiocarcinoma, stomach cancer, and pancreatic cancer). From the receiver operating characteristic analysis in HCC, both sensitivity and specificity were shown to be greater than 70.0 and 85.0%, respectively. Thus, the high-resolution proteomic approach demonstrates that hCE1 is a good candidate for further validation as a serologic glycoprotein biomarker for HCC.
authors: Graduate Program in Functional Genomics, Yonsei Proteome Research Center and Biomedical Proteome Research Center, Yonsei University, Seoul 120-749, Korea.
authors: Keun
authors: K
authors: Na
authors: Eun-Young
authors: EY
authors: Lee
authors: Hyoung-Joo
authors: HJ
authors: Lee
authors: Kwang-Youl
authors: KY
authors: Kim
authors: Hanna
authors: H
authors: Lee
authors: Seul-Ki
authors: SK
authors: Jeong
authors: An-Sung
authors: AS
authors: Jeong
authors: Sang Yun
authors: SY
authors: Cho
authors: Sun A
authors: SA
authors: Kim
authors: Si Young
authors: SY
authors: Song
authors: Kyung Sik
authors: KS
authors: Kim
authors: Sung Won
authors: SW
authors: Cho
authors: Hoguen
authors: H
authors: Kim
authors: Young-Ki
authors: YK
authors: Paik
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D015153:Blotting, Western; D002265:Carboxylic Ester Hydrolases / Q000097:blood* / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000201:enzymology*; D002853:Chromatography, Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000097:blood* / Q000201:enzymology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor; D006023:Glycoproteins; D002265:Carboxylic Ester Hydrolases; C474609:CES1 protein, human