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LC-MS profiling of N-Glycans derived from human serum samples for biomarker discovery in hepatocellular carcinoma.

Tsai TH, Wang M, Di Poto C, Hu Y, Zhou S, Zhao Y, Varghese RS, Luo Y, Tadesse MG, Ziada DH, Desai CS, Shetty K, Mechref Y, Ressom HW - J. Proteome Res. (2014)

Bottom Line: Through two complementary LC-ESI-MS quantitation approaches, global profiling and targeted quantitation, we identified 11 N-glycans with statistically significant differences between HCC cases and cirrhotic controls.These glycans can further be categorized into four structurally related clusters, matching closely with the implications of important glycosyltransferases in cancer progression and metastasis.The results of this study illustrate the power of the integrative approach combining complementary LC-ESI-MS based quantitation approaches to investigate changes in N-glycan levels between HCC cases and patients with liver cirrhosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center , Washington, DC 20057, United States.

ABSTRACT
Defining clinically relevant biomarkers for early stage hepatocellular carcinoma (HCC) in a high-risk population of cirrhotic patients has potentially far-reaching implications for disease management and patient health. Changes in glycan levels have been associated with the onset of numerous diseases including cancer. In the present study, we used liquid chromatography coupled with electrospray ionization mass spectrometry (LC-ESI-MS) to analyze N-glycans in sera from 183 participants recruited in Egypt and the U.S. and identified candidate biomarkers that distinguish HCC cases from cirrhotic controls. N-Glycans were released from serum proteins and permethylated prior to the LC-ESI-MS analysis. Through two complementary LC-ESI-MS quantitation approaches, global profiling and targeted quantitation, we identified 11 N-glycans with statistically significant differences between HCC cases and cirrhotic controls. These glycans can further be categorized into four structurally related clusters, matching closely with the implications of important glycosyltransferases in cancer progression and metastasis. The results of this study illustrate the power of the integrative approach combining complementary LC-ESI-MS based quantitation approaches to investigate changes in N-glycan levels between HCC cases and patients with liver cirrhosis.

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Four clusters of theidentified N-glycan candidate biomarkers andtheir FC directions.
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fig4: Four clusters of theidentified N-glycan candidate biomarkers andtheir FC directions.

Mentions: Biosynthesis of N-glycans in the Golgi apparatus involvestrimmingof mannose residuals and stepwise addition of monosaccharides, resultingin three groups of N-glycans: high-mannose, complex, and hybrid types.Most of the candidate biomarkers identified in this study are complextype N-glycans with two hybrid-type glycans: [3-4-1-0-0] and [6-6-0-1-2].Some biomarker discovery studies for other types of cancer have shownthat structurally related glycans are likely to have correlated changesof levels due to the same biosynthesis process they are involved in.14 Our study exhibited a similar phenomenon, wheremany of the candidate biomarkers for HCC are closely related in theirstructures. These glycans can be grouped into four clusters: Cluster1, biantennary structure; Cluster 2, β-1,6-GlcNAc branchingstructure (down-regulated); Cluster 3, β-1,6-GlcNAc branchingstructure (up-regulated); and Cluster 4, tetra-antennary structureas shown in Figure 4. Within each cluster theglycans show consistent changes in their levels.


LC-MS profiling of N-Glycans derived from human serum samples for biomarker discovery in hepatocellular carcinoma.

Tsai TH, Wang M, Di Poto C, Hu Y, Zhou S, Zhao Y, Varghese RS, Luo Y, Tadesse MG, Ziada DH, Desai CS, Shetty K, Mechref Y, Ressom HW - J. Proteome Res. (2014)

Four clusters of theidentified N-glycan candidate biomarkers andtheir FC directions.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4227556&req=5

fig4: Four clusters of theidentified N-glycan candidate biomarkers andtheir FC directions.
Mentions: Biosynthesis of N-glycans in the Golgi apparatus involvestrimmingof mannose residuals and stepwise addition of monosaccharides, resultingin three groups of N-glycans: high-mannose, complex, and hybrid types.Most of the candidate biomarkers identified in this study are complextype N-glycans with two hybrid-type glycans: [3-4-1-0-0] and [6-6-0-1-2].Some biomarker discovery studies for other types of cancer have shownthat structurally related glycans are likely to have correlated changesof levels due to the same biosynthesis process they are involved in.14 Our study exhibited a similar phenomenon, wheremany of the candidate biomarkers for HCC are closely related in theirstructures. These glycans can be grouped into four clusters: Cluster1, biantennary structure; Cluster 2, β-1,6-GlcNAc branchingstructure (down-regulated); Cluster 3, β-1,6-GlcNAc branchingstructure (up-regulated); and Cluster 4, tetra-antennary structureas shown in Figure 4. Within each cluster theglycans show consistent changes in their levels.

Bottom Line: Through two complementary LC-ESI-MS quantitation approaches, global profiling and targeted quantitation, we identified 11 N-glycans with statistically significant differences between HCC cases and cirrhotic controls.These glycans can further be categorized into four structurally related clusters, matching closely with the implications of important glycosyltransferases in cancer progression and metastasis.The results of this study illustrate the power of the integrative approach combining complementary LC-ESI-MS based quantitation approaches to investigate changes in N-glycan levels between HCC cases and patients with liver cirrhosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center , Washington, DC 20057, United States.

ABSTRACT
Defining clinically relevant biomarkers for early stage hepatocellular carcinoma (HCC) in a high-risk population of cirrhotic patients has potentially far-reaching implications for disease management and patient health. Changes in glycan levels have been associated with the onset of numerous diseases including cancer. In the present study, we used liquid chromatography coupled with electrospray ionization mass spectrometry (LC-ESI-MS) to analyze N-glycans in sera from 183 participants recruited in Egypt and the U.S. and identified candidate biomarkers that distinguish HCC cases from cirrhotic controls. N-Glycans were released from serum proteins and permethylated prior to the LC-ESI-MS analysis. Through two complementary LC-ESI-MS quantitation approaches, global profiling and targeted quantitation, we identified 11 N-glycans with statistically significant differences between HCC cases and cirrhotic controls. These glycans can further be categorized into four structurally related clusters, matching closely with the implications of important glycosyltransferases in cancer progression and metastasis. The results of this study illustrate the power of the integrative approach combining complementary LC-ESI-MS based quantitation approaches to investigate changes in N-glycan levels between HCC cases and patients with liver cirrhosis.

Show MeSH
Related in: MedlinePlus