Human plasma carboxylesterase 1, a novel serologic biomarker candidate for hepatocellular carcinoma

Keun Na, Eun Young Lee, Hyoung Joo Lee, Kwang Youl Kim, Hanna Lee, Seul Ki Jeong, An Sung Jeong, Yun Cho Sang, Sun A. Kim, Young Song Si, Sik Kim Kyung, Won Cho Sung, Hoguen Kim, Young-Ki Paik

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)3989-3999
Number of pages11
JournalProteomics
Volume9
Issue number16
DOIs
Publication statusPublished - 2009 Aug 1

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Plasma (human)
Carboxylesterase
Biomarkers
Hepatocellular Carcinoma
Glycoproteins
Tissue
Tumors
Immunoprecipitation
Liver
Western Blotting
Plasmas
Affinity chromatography
Neoplasms
Cholangiocarcinoma
Chronic Hepatitis
Pancreatic Neoplasms
Affinity Chromatography
Lectins
ROC Curve
Liver Cirrhosis

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

Na, Keun ; Lee, Eun Young ; Lee, Hyoung Joo ; Kim, Kwang Youl ; Lee, Hanna ; Jeong, Seul Ki ; Jeong, An Sung ; Sang, Yun Cho ; Kim, Sun A. ; Si, Young Song ; Kyung, Sik Kim ; Sung, Won Cho ; Kim, Hoguen ; Paik, Young-Ki. / Human plasma carboxylesterase 1, a novel serologic biomarker candidate for hepatocellular carcinoma. In: Proteomics. 2009 ; Vol. 9, No. 16. pp. 3989-3999.
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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.",
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Na, K, Lee, EY, Lee, HJ, Kim, KY, Lee, H, Jeong, SK, Jeong, AS, Sang, YC, Kim, SA, Si, YS, Kyung, SK, Sung, WC, Kim, H & Paik, Y-K 2009, 'Human plasma carboxylesterase 1, a novel serologic biomarker candidate for hepatocellular carcinoma', Proteomics, vol. 9, no. 16, pp. 3989-3999. https://doi.org/10.1002/pmic.200900105

Human plasma carboxylesterase 1, a novel serologic biomarker candidate for hepatocellular carcinoma. / Na, Keun; Lee, Eun Young; Lee, Hyoung Joo; Kim, Kwang Youl; Lee, Hanna; Jeong, Seul Ki; Jeong, An Sung; Sang, Yun Cho; Kim, Sun A.; Si, Young Song; Kyung, Sik Kim; Sung, Won Cho; Kim, Hoguen; Paik, Young-Ki.

In: Proteomics, Vol. 9, No. 16, 01.08.2009, p. 3989-3999.

Research output: Contribution to journalArticle

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AU - Na, Keun

AU - Lee, Eun Young

AU - Lee, Hyoung Joo

AU - Kim, Kwang Youl

AU - Lee, Hanna

AU - Jeong, Seul Ki

AU - Jeong, An Sung

AU - Sang, Yun Cho

AU - Kim, Sun A.

AU - Si, Young Song

AU - Kyung, Sik Kim

AU - Sung, Won Cho

AU - Kim, Hoguen

AU - Paik, Young-Ki

PY - 2009/8/1

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N2 - 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.

AB - 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.

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