Human plasma carboxylesterase 1, a novel serologic biomarker candidate for hepatocellular carcinoma.
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.
Na
Keun
K
Graduate Program in Functional Genomics, Yonsei Proteome Research Center and Biomedical Proteome Research Center, Yonsei University, Seoul 120-749, Korea.
Lee
Eun-Young
EY
Lee
Hyoung-Joo
HJ
Kim
Kwang-Youl
KY
Lee
Hanna
H
Jeong
Seul-Ki
SK
Jeong
An-Sung
AS
Cho
Sang Yun
SY
Kim
Sun A
SA
Song
Si Young
SY
Kim
Kyung Sik
KS
Cho
Sung Won
SW
Kim
Hoguen
H
Paik
Young-Ki
YK
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
D014408:Biomarkers, Tumor; D006023:Glycoproteins; D002265:Carboxylic Ester Hydrolases; C474609:CES1 protein, human