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Lectin-based glycoproteomics to explore and analyze hepatocellular carcinoma-related glycoprotein markers

期刊

ELECTROPHORESIS
卷 30, 期 17, 页码 2957-2966

出版社

WILEY
DOI: 10.1002/elps.200900064

关键词

2-DE; Biomarkers; Glycoproteomics; Hepatocellular carcinoma; Lectin

资金

  1. State 863 High Technology R&D Project of China [2007AA02Z479]
  2. Program for Outstanding Medical Academic Leader [LJ06004]
  3. Specialized Research Fund for the Doctoral Program of Higher Education [20070246112]

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More and more new diagnostic biomarkers of hepatocellular carcinoma (HCC) have been found in association with advances in the standardization of 2-DE coupled with MS analysis. However, the diagnosis of HCC is still detected in the late stages of the disease, when treatment options are limited and prognosis is poor. The glycosylation of proteins is known to change in tumor cells during the development of HCC as the result of alterations in the levels of glycosyltransferases, such as increased fucosylation of Golgi Protein 73 and alpha-fetoprotein. These structural changes can influence the function or physiochemical proper-ties of a protein, resulting in abnormal cancer cell behavior. Therefore, identification of HCC-related glycoprotein markers and analysis of glycan structural alterations might assist in the early detection of HCC. Here, we summarize lectin-based glycoproteomic strategies for the discovery of relevant biomarkers of HCC. The carbohydrate-binding specificities of different lectins offer a biological affinity approach that complements existing MS capabilities. These strategies involve the enrichment of glycoproteins or glycopeptides by lectins, followed by releasing carbohydrates with peptide-N-glycosidase F or reductive beta-elimination. The obtained glycopeptides are then identified by automated MS/MS and structural analysis of glycans is per-formed through modern methods such as quadrupole IT-TOF, MALDI-TOF/TOF and lectin microarray. These strategies will lead to faster and more clinically adaptable tests with greater sensitivity and specificity.

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