Journal
JOURNAL OF PROTEOME RESEARCH
Volume 9, Issue 2, Pages 798-805Publisher
AMER CHEMICAL SOC
DOI: 10.1021/pr900715p
Keywords
Glycoproteins; Hepatocellular; Cancer; Lectin arrays; Biomarkers; Mass Spectrometry
Categories
Funding
- National Cancer Institute [R01 CA106402, R21 CA124441]
- National Institutes of Health [R01GM49500, R01-DK066840, R03 DK077707]
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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.
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