Identification and confirmation of biomarkers using an integrated platform for quantitative analysis of glycoproteins and their glycosylations

Yashu Liu, Jintang He, Chen Li, Ricardo Benitez, Sherry Fu, Jorge Marrero, David M. Lubman

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. However, accurate diagnosis can be difficult as most of the patients who develop this tumor have symptoms similar to those caused by longstanding liver disease. Herein we developed an integrated platform to discover the glycoprotein biomarkers in early HCC. At first, lectin arrays were applied to investigate the differences in glycan structures on serum glycoproteins from HCC and cirrhosis patients. The intensity for AAL and LCA was significantly higher in HCC, indicating an elevation of fucosylation level. Then serum from 10 HCC samples and 10 cirrhosis samples were used to screen the altered fucosylated proteins by a combination of Exactag labeling, lectin extraction and LC-MS/MS. Finally, 27 HCC and 27 cirrhosis serum samples were used for lectin-antibody arrays to confirm the change of these fucosylated proteins. C3, CE, HRG, CD14 and HGF were found to be biomarker candidates for distinguishing early HCC from cirrhosis, with a sensitivity of 72% and specificity of 79%. Our work gives insight to the detection of early HCC, and the application of this comprehensive strategy has the potential to facilitate biomarker discovery on a large scale.

Original languageEnglish (US)
Pages (from-to)798-805
Number of pages8
JournalJournal of Proteome Research
Volume9
Issue number2
DOIs
StatePublished - Feb 5 2010

Fingerprint

Glycosylation
Biomarkers
Lectins
Hepatocellular Carcinoma
Glycoproteins
Liver
Tumors
Chemical analysis
Fibrosis
Labeling
Polysaccharides
Proteins
Antibodies
Serum
Liver Diseases
Neoplasms
Sensitivity and Specificity

Keywords

  • Biomarkers
  • Cancer
  • Glycoproteins
  • Hepatocellular
  • Lectin arrays
  • Mass spectrometry

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Identification and confirmation of biomarkers using an integrated platform for quantitative analysis of glycoproteins and their glycosylations. / Liu, Yashu; He, Jintang; Li, Chen; Benitez, Ricardo; Fu, Sherry; Marrero, Jorge; Lubman, David M.

In: Journal of Proteome Research, Vol. 9, No. 2, 05.02.2010, p. 798-805.

Research output: Contribution to journalArticle

Liu, Yashu ; He, Jintang ; Li, Chen ; Benitez, Ricardo ; Fu, Sherry ; Marrero, Jorge ; Lubman, David M. / Identification and confirmation of biomarkers using an integrated platform for quantitative analysis of glycoproteins and their glycosylations. In: Journal of Proteome Research. 2010 ; Vol. 9, No. 2. pp. 798-805.
@article{96799627514e4b4f83bec9e214e8137d,
title = "Identification and confirmation of biomarkers using an integrated platform for quantitative analysis of glycoproteins and their glycosylations",
abstract = "Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. However, accurate diagnosis can be difficult as most of the patients who develop this tumor have symptoms similar to those caused by longstanding liver disease. Herein we developed an integrated platform to discover the glycoprotein biomarkers in early HCC. At first, lectin arrays were applied to investigate the differences in glycan structures on serum glycoproteins from HCC and cirrhosis patients. The intensity for AAL and LCA was significantly higher in HCC, indicating an elevation of fucosylation level. Then serum from 10 HCC samples and 10 cirrhosis samples were used to screen the altered fucosylated proteins by a combination of Exactag labeling, lectin extraction and LC-MS/MS. Finally, 27 HCC and 27 cirrhosis serum samples were used for lectin-antibody arrays to confirm the change of these fucosylated proteins. C3, CE, HRG, CD14 and HGF were found to be biomarker candidates for distinguishing early HCC from cirrhosis, with a sensitivity of 72{\%} and specificity of 79{\%}. Our work gives insight to the detection of early HCC, and the application of this comprehensive strategy has the potential to facilitate biomarker discovery on a large scale.",
keywords = "Biomarkers, Cancer, Glycoproteins, Hepatocellular, Lectin arrays, Mass spectrometry",
author = "Yashu Liu and Jintang He and Chen Li and Ricardo Benitez and Sherry Fu and Jorge Marrero and Lubman, {David M.}",
year = "2010",
month = "2",
day = "5",
doi = "10.1021/pr900715p",
language = "English (US)",
volume = "9",
pages = "798--805",
journal = "Journal of Proteome Research",
issn = "1535-3893",
publisher = "American Chemical Society",
number = "2",

}

TY - JOUR

T1 - Identification and confirmation of biomarkers using an integrated platform for quantitative analysis of glycoproteins and their glycosylations

AU - Liu, Yashu

AU - He, Jintang

AU - Li, Chen

AU - Benitez, Ricardo

AU - Fu, Sherry

AU - Marrero, Jorge

AU - Lubman, David M.

PY - 2010/2/5

Y1 - 2010/2/5

N2 - Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. However, accurate diagnosis can be difficult as most of the patients who develop this tumor have symptoms similar to those caused by longstanding liver disease. Herein we developed an integrated platform to discover the glycoprotein biomarkers in early HCC. At first, lectin arrays were applied to investigate the differences in glycan structures on serum glycoproteins from HCC and cirrhosis patients. The intensity for AAL and LCA was significantly higher in HCC, indicating an elevation of fucosylation level. Then serum from 10 HCC samples and 10 cirrhosis samples were used to screen the altered fucosylated proteins by a combination of Exactag labeling, lectin extraction and LC-MS/MS. Finally, 27 HCC and 27 cirrhosis serum samples were used for lectin-antibody arrays to confirm the change of these fucosylated proteins. C3, CE, HRG, CD14 and HGF were found to be biomarker candidates for distinguishing early HCC from cirrhosis, with a sensitivity of 72% and specificity of 79%. Our work gives insight to the detection of early HCC, and the application of this comprehensive strategy has the potential to facilitate biomarker discovery on a large scale.

AB - Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. However, accurate diagnosis can be difficult as most of the patients who develop this tumor have symptoms similar to those caused by longstanding liver disease. Herein we developed an integrated platform to discover the glycoprotein biomarkers in early HCC. At first, lectin arrays were applied to investigate the differences in glycan structures on serum glycoproteins from HCC and cirrhosis patients. The intensity for AAL and LCA was significantly higher in HCC, indicating an elevation of fucosylation level. Then serum from 10 HCC samples and 10 cirrhosis samples were used to screen the altered fucosylated proteins by a combination of Exactag labeling, lectin extraction and LC-MS/MS. Finally, 27 HCC and 27 cirrhosis serum samples were used for lectin-antibody arrays to confirm the change of these fucosylated proteins. C3, CE, HRG, CD14 and HGF were found to be biomarker candidates for distinguishing early HCC from cirrhosis, with a sensitivity of 72% and specificity of 79%. Our work gives insight to the detection of early HCC, and the application of this comprehensive strategy has the potential to facilitate biomarker discovery on a large scale.

KW - Biomarkers

KW - Cancer

KW - Glycoproteins

KW - Hepatocellular

KW - Lectin arrays

KW - Mass spectrometry

UR - http://www.scopus.com/inward/record.url?scp=76149089532&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=76149089532&partnerID=8YFLogxK

U2 - 10.1021/pr900715p

DO - 10.1021/pr900715p

M3 - Article

VL - 9

SP - 798

EP - 805

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 2

ER -