Grant Number:	5R01CA135069-02 Interpret this number
Primary Investigator:	Goldman, Radoslav
Organization:	Georgetown University
Project Title:	Glycans in Hepatocellular Carcinoma
Fiscal Year:	2010

DESCRIPTION (provided by applicant): Early detection of cancer and precancerous conditions improves patient survival. This study will identify changes in protein associated glycans associated with the development of hepatocellular carcinoma. To achieve this goal, we developed mass spectrometric analysis of permethylated glycans enzymatically removed from serum proteins. This method allows an efficient and high-throughput comparison of glycans. We tested the method on a pilot set of hepatocellular carcinoma cases and controls from our unique study of hepatocellular carcinoma in Egypt, a country with an epidemic of hepatitis C viral infection. The pilot-study identified three glycans that predict hepatocellular carcinoma with 90% prediction accuracy compared to controls with chronic liver disease. In this study, we propose to expand the project and to include a comparison of hepatocellular carcinoma cases and chronic liver disease controls in the US population. As we continue to assess glycan changes in the progression of chronic viral infection to hepatocellular carcinoma, we will continue to improve the analytical methods for quantification and structural characterization of the glycans. It is expected that the quantification of glycans will improve the performance of currently available methods for early detection of hepatocellular carcinoma. Defining clinically applicable markers of early-stage cancer has potentially far-reaching consequences for disease management and patient health. The glycan markers could be used to screen high risk populations for early signs of disease; to design and test new chemoprevention strategies; and to follow disease progression after treatment. Identification of the changes in glycans associated with disease progression is expected to generate new hypotheses for carcinogenesis of the liver. PUBLIC HEALTH RELEVANCE: Early detection of cancer and precancerous conditions improves patient survival. This study will identify changes in various protein-decorating sugars that accompany the development of liver cancer. To achieve this goal, we developed methods that allow high-throughput comparison of these sugars. The identified sugars could be used to screen high risk populations for early signs of liver cancer; to design and test new chemoprevention strategies; and to follow disease progression after treatment.




A multiplexed microflow LC-MS/MS-PRM assay for serologic quantification of IgG N- and HPX O- glycoforms in liver fibrosis.
Authors: Panigrahi A. , Zhang L. , Benicky J. , Sanda M. , Ahn J. , Goldman R. .
Source: Scientific Reports, 2023-01-12 00:00:00.0; 13(1), p. 606.
EPub date: 2023-01-12 00:00:00.0.
PMID: 36635317
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Extracellular Heparan 6-O-Endosulfatases SULF1 and SULF2 in Head and Neck Squamous Cell Carcinoma and Other Malignancies.
Authors: Yang Y. , Ahn J. , Edwards N.J. , Benicky J. , Rozeboom A.M. , Davidson B. , Karamboulas C. , Nixon K.C.J. , Ailles L. , Goldman R. .
Source: Cancers, 2022-11-11 00:00:00.0; 14(22), .
EPub date: 2022-11-11 00:00:00.0.
PMID: 36428645
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LC-MS/MS-PRM Quantification of IgG glycoforms using stable isotope labeled IgG1 Fc glycopeptide standard.
Authors: Sanda M. , Yang Q. , Zong G. , Chen H. , Zheng Z. , Dhani H. , Khan K. , Kroemer A. , Wang L.X. , Goldman R. .
Source: Biorxiv : The Preprint Server For Biology, 2022-08-02 00:00:00.0; , .
EPub date: 2022-08-02 00:00:00.0.
PMID: 35982648
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A Rapid LC-MS/MS-PRM Assay for Serologic Quantification of Sialylated O-HPX Glycoforms in Patients with Liver Fibrosis.
Authors: Panigrahi A. , Benicky J. , Wei R. , Ahn J. , Goldman R. , Sanda M. .
Source: Molecules (basel, Switzerland), 2022-03-29 00:00:00.0; 27(7), .
EPub date: 2022-03-29 00:00:00.0.
PMID: 35408612
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Analysis of site and structure specific core fucosylation in liver cirrhosis using exoglycosidase-assisted data-independent LC-MS/MS.
Authors: Sanda M. , Ahn J. , Kozlik P. , Goldman R. .
Source: Scientific Reports, 2021-12-02 00:00:00.0; 11(1), p. 23273.
EPub date: 2021-12-02 00:00:00.0.
PMID: 34857845
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PD-L1 Glycosylation and Its Impact on Binding to Clinical Antibodies.
Authors: Benicky J. , Sanda M. , Brnakova Kennedy Z. , Grant O.C. , Woods R.J. , Zwart A. , Goldman R. .
Source: Journal Of Proteome Research, 2021-01-01 00:00:00.0; 20(1), p. 485-497.
EPub date: 2020-10-19 00:00:00.0.
PMID: 33073996
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A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women.
Authors: McIntosh A.T. , Wei R. , Ahn J. , Aouizerat B.E. , Kassaye S.G. , Augenbraun M.H. , Price J.C. , French A.L. , Gange S.J. , Anastos K.M. , et al. .
Source: Plos One, 2021; 16(3), p. e0247277.
EPub date: 2021-03-11 00:00:00.0.
PMID: 33705408
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Glycan-specific precipitation of glycopeptides in high organic content sample solvents used in HILIC.
Authors: Kozlik P. , Molnarova K. , Jecmen T. , Krizek T. , Goldman R. .
Source: Journal Of Chromatography. B, Analytical Technologies In The Biomedical And Life Sciences, 2020-08-01 00:00:00.0; 1150, p. 122196.
EPub date: 2020-05-28 00:00:00.0.
PMID: 32485649
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Low Collision Energy Fragmentation in Structure-Specific Glycoproteomics Analysis.
Authors: Sanda M. , Benicky J. , Goldman R. .
Source: Analytical Chemistry, 2020-06-16 00:00:00.0; 92(12), p. 8262-8267.
EPub date: 2020-06-04 00:00:00.0.
PMID: 32441515
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N-Glycosylation is required for secretion of the precursor to brain-derived neurotrophic factor (proBDNF) carrying sulfated LacdiNAc structures.
Authors: Benicky J. , Sanda M. , Brnakova Kennedy Z. , Goldman R. .
Source: The Journal Of Biological Chemistry, 2019-11-08 00:00:00.0; 294(45), p. 16816-16830.
EPub date: 2019-09-26 00:00:00.0.
PMID: 31558607
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Optimized Fragmentation for Quantitative Analysis of Fucosylated N-Glycoproteins by LC-MS-MRM.
Authors: Yuan W. , Wei R. , Goldman R. , Sanda M. .
Source: Analytical Chemistry, 2019-07-16 00:00:00.0; 91(14), p. 9206-9212.
EPub date: 2019-07-03 00:00:00.0.
PMID: 31268672
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Proteomic alterations of HDL in youth with type 1 diabetes and their associations with glycemic control: a case-control study.
Authors: Gourgari E. , Ma J. , Playford M.P. , Mehta N.N. , Goldman R. , Remaley A.T. , Gordon S.M. .
Source: Cardiovascular Diabetology, 2019-03-28 00:00:00.0; 18(1), p. 43.
EPub date: 2019-03-28 00:00:00.0.
PMID: 30922315
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Quantitative analysis of core fucosylation of serum proteins in liver diseases by LC-MS-MRM.
Authors: Ma J. , Sanda M. , Wei R. , Zhang L. , Goldman R. .
Source: Journal Of Proteomics, 2018-10-30 00:00:00.0; 189, p. 67-74.
EPub date: 2018-02-07 00:00:00.0.
PMID: 29427759
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Quantitative Analysis of Sex-Hormone-Binding Globulin Glycosylation in Liver Diseases by Liquid Chromatography-Mass Spectrometry Parallel Reaction Monitoring.
Authors: Yuan W. , Benicky J. , Wei R. , Goldman R. , Sanda M. .
Source: Journal Of Proteome Research, 2018-08-03 00:00:00.0; 17(8), p. 2755-2766.
EPub date: 2018-07-16 00:00:00.0.
PMID: 29972295
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Hydrophilic interaction liquid chromatography in the separation of glycopeptides and their isomers.
Authors: Kozlik P. , Goldman R. , Sanda M. .
Source: Analytical And Bioanalytical Chemistry, 2018-05-28 00:00:00.0; , .
EPub date: 2018-05-28 00:00:00.0.
PMID: 29806066
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Loss and gain of N-linked glycosylation sequons due to single-nucleotide variation in cancer.
Authors: Fan Y. , Hu Y. , Yan C. , Goldman R. , Pan Y. , Mazumder R. , Dingerdissen H.M. .
Source: Scientific Reports, 2018-03-12 00:00:00.0; 8(1), p. 4322.
EPub date: 2018-03-12 00:00:00.0.
PMID: 29531238
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Nano reversed phase versus nano hydrophilic interaction liquid chromatography on a chip in the analysis of hemopexin glycopeptides.
Authors: Kozlik P. , Sanda M. , Goldman R. .
Source: Journal Of Chromatography. A, 2017-10-13 00:00:00.0; 1519, p. 152-155.
EPub date: 2017-08-26 00:00:00.0.
PMID: 28888681
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Changes in the Glycosylation of Kininogen and the Development of a Kininogen-Based Algorithm for the Early Detection of HCC.
Authors: Wang M. , Sanda M. , Comunale M.A. , Herrera H. , Swindell C. , Kono Y. , Singal A.G. , Marrero J. , Block T. , Goldman R. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2017 May; 26(5), p. 795-803.
EPub date: 2017-02-21 00:00:00.0.
PMID: 28223431
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Study of structure-dependent chromatographic behavior of glycopeptides using reversed phase nanoLC.
Authors: Kozlik P. , Goldman R. , Sanda M. .
Source: Electrophoresis, 2017-04-26 00:00:00.0; , .
EPub date: 2017-04-26 00:00:00.0.
PMID: 28444931
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Changes in the expression of N- and O-glycopeptides in patients with colorectal cancer and hepatocellular carcinoma quantified by full-MS scan FT-ICR and multiple reaction monitoring.
Authors: Darebna P. , Novak P. , Kucera R. , Topolcan O. , Sanda M. , Goldman R. , Pompach P. .
Source: Journal Of Proteomics, 2017-02-05 00:00:00.0; 153, p. 44-52.
EPub date: 2016-09-16 00:00:00.0.
PMID: 27646713
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Site-specific Analysis Of Changes In The Glycosylation Of Proteins In Liver Cirrhosis Using Data-independent Workflow With Soft Fragmentation
Authors: Sanda M. , Zhang L. , Edwards N.J. , Goldman R. .
Source: Analytical And Bioanalytical Chemistry, 2017 Jan; 409(2), p. 619-627.
PMID: 27822650
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Data Independent Analysis of IgG Glycoforms in Samples of Unfractionated Human Plasma.
Authors: Sanda M. , Goldman R. .
Source: Analytical Chemistry, 2016-10-18 00:00:00.0; 88(20), p. 10118-10125.
EPub date: 2016-09-29 00:00:00.0.
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Expression of the extracellular sulfatase SULF2 is associated with squamous cell carcinoma of the head and neck.
Authors: Flowers S.A. , Zhou X. , Wu J. , Wang Y. , Makambi K. , Kallakury B.V. , Singer M.S. , Rosen S.D. , Davidson B. , Goldman R. .
Source: Oncotarget, 2016-07-12 00:00:00.0; 7(28), p. 43177-43187.
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Increased Sialylation Of Site Specific O-glycoforms Of Hemopexin In Liver Disease
Authors: Sanda M. , Benicky J. , Wu J. , Wang Y. , Makambi K. , Ahn J. , Smith C.I. , Zhao P. , Zhang L. , Goldman R. .
Source: Clinical Proteomics, 2016; 13, p. 24.
PMID: 27688741
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Quantitative Analysis Of Immunoglobulin Subclasses And Subclass Specific Glycosylation By Lc-ms-mrm In Liver Disease
Authors: Yuan W. , Sanda M. , Wu J. , Koomen J. , Goldman R. .
Source: Journal Of Proteomics, 2015-02-26 00:00:00.0; 116, p. 24-33.
PMID: 25582524
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Sulf2, A Heparan Sulfate Endosulfatase, Is Present In The Blood Of Healthy Individuals And Increases In Cirrhosis
Authors: Singer M.S. , Phillips J.J. , Lemjabbar-Alaoui H. , Wang Y.Q. , Wu J. , Goldman R. , Rosen S.D. .
Source: Clinica Chimica Acta; International Journal Of Clinical Chemistry, 2015-02-02 00:00:00.0; 440, p. 72-8.
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Targeted Methods For Quantitative Analysis Of Protein Glycosylation
Authors: Goldman R. , Sanda M. .
Source: Proteomics. Clinical Applications, 2015 Feb; 9(1-2), p. 17-32.
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Structure-function Analysis Of Hepatitis C Virus Envelope Glycoproteins E1 And E2
Authors: Nayak A. , Pattabiraman N. , Fadra N. , Goldman R. , Kosakovsky Pond S.L. , Mazumder R. .
Source: Journal Of Biomolecular Structure & Dynamics, 2015; 33(8), p. 1682-94.
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Protein And Site Specificity Of Fucosylation In Liver-secreted Glycoproteins
Authors: Pompach P. , Ashline D.J. , Brnakova Z. , Benicky J. , Sanda M. , Goldman R. .
Source: Journal Of Proteome Research, 2014-12-05 00:00:00.0; 13(12), p. 5561-9.
PMID: 25265424
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Quantification Of Fucosylated Hemopexin And Complement Factor H In Plasma Of Patients With Liver Disease
Authors: Benicky J. , Sanda M. , Pompach P. , Wu J. , Goldman R. .
Source: Analytical Chemistry, 2014-11-04 00:00:00.0; 86(21), p. 10716-23.
PMID: 25302577
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Site-specific Glycan Microheterogeneity Of Inter-alpha-trypsin Inhibitor Heavy Chain H4
Authors: Chandler K.B. , Brnakova Z. , Sanda M. , Wang S. , Stalnaker S.H. , Bridger R. , Zhao P. , Wells L. , Edwards N.J. , Goldman R. .
Source: Journal Of Proteome Research, 2014-07-03 00:00:00.0; 13(7), p. 3314-29.
PMID: 24884609
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Sex hormone pathway gene polymorphisms are associated with risk of advanced hepatitis C-related liver disease in males.
Authors: White D.L. , Liu Y. , Garcia J. , El-Serag H.B. , Jiao L. , Tsavachidis S. , Franco L.M. , Lee J.S. , Tavakoli-Tabasi S. , Moore D. , et al. .
Source: International Journal Of Molecular Epidemiology And Genetics, 2014; 5(3), p. 164-76.
EPub date: 2014-10-22 00:00:00.0.
PMID: 25379136
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A Click Chemistry Approach to Identify Protein Targets of Cancer Chemopreventive Phenethyl Isothiocyanate.
Authors: Fu Y. , Mi L. , Sanda M. , Silverstein S. , Aggarwal M. , Wang D. , Gupta P. , Goldman R. , Appella D.H. , Chung F.L. .
Source: Rsc Advances, 2014; 4(8), p. 3920-3923.
PMID: 28725420
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Exploring Site-specific N-glycosylation Microheterogeneity Of Haptoglobin Using Glycopeptide Cid Tandem Mass Spectra And Glycan Database Search
Authors: Chandler K.B. , Pompach P. , Goldman R. , Edwards N. .
Source: Journal Of Proteome Research, 2013-08-02 00:00:00.0; 12(8), p. 3652-66.
PMID: 23829323
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Lc-ms3 Quantification Of O-glycopeptides In Human Serum
Authors: Sanda M. , Pompach P. , Benicky J. , Goldman R. .
Source: Electrophoresis, 2013 Aug; 34(16), p. 2342-9.
PMID: 23765987
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Quantitative Liquid Chromatography-mass Spectrometry-multiple Reaction Monitoring (lc-ms-mrm) Analysis Of Site-specific Glycoforms Of Haptoglobin In Liver Disease
Authors: Sanda M. , Pompach P. , Brnakova Z. , Wu J. , Makambi K. , Goldman R. .
Source: Molecular & Cellular Proteomics : Mcp, 2013 May; 12(5), p. 1294-305.
PMID: 23389048
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Site-specific Glycoforms Of Haptoglobin In Liver Cirrhosis And Hepatocellular Carcinoma
Authors: Pompach P. , Brnakova Z. , Sanda M. , Wu J. , Edwards N. , Goldman R. .
Source: Molecular & Cellular Proteomics : Mcp, 2013 May; 12(5), p. 1281-93.
PMID: 23389049
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Glycoprotein Disease Markers And Single Protein-omics
Authors: Chandler K. , Goldman R. .
Source: Molecular & Cellular Proteomics : Mcp, 2013 Apr; 12(4), p. 836-45.
PMID: 23399550
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Structure-based Comparative Analysis And Prediction Of N-linked Glycosylation Sites In Evolutionarily Distant Eukaryotes
Authors: Lam P.V. , Goldman R. , Karagiannis K. , Narsule T. , Simonyan V. , Soika V. , Mazumder R. .
Source: Genomics, Proteomics & Bioinformatics, 2013 Apr; 11(2), p. 96-104.
PMID: 23459159
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Analysis Of Peptides By Denaturing Ultrafiltration And Lc-maldi-tof-ms
Authors: An Y. , Goldman R. .
Source: Methods In Molecular Biology (clifton, N.j.), 2013; 1023, p. 13-9.
PMID: 23765617
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Utilization Of Metabolomics To Identify Serum Biomarkers For Hepatocellular Carcinoma In Patients With Liver Cirrhosis
Authors: Ressom H.W. , Xiao J.F. , Tuli L. , Varghese R.S. , Zhou B. , Tsai T.H. , Ranjbar M.R. , Zhao Y. , Wang J. , Di Poto C. , et al. .
Source: Analytica Chimica Acta, 2012-09-19 00:00:00.0; 743, p. 90-100.
PMID: 22882828
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N-glycans In Liver-secreted And Immunoglogulin-derived Protein Fractions
Authors: Bekesova S. , Kosti O. , Chandler K.B. , Wu J. , Madej H.L. , Brown K.C. , Simonyan V. , Goldman R. .
Source: Journal Of Proteomics, 2012-04-03 00:00:00.0; 75(7), p. 2216-24.
PMID: 22326963
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Semi-automated Identification Of N-glycopeptides By Hydrophilic Interaction Chromatography, Nano-reverse-phase Lc-ms/ms, And Glycan Database Search
Authors: Pompach P. , Chandler K.B. , Lan R. , Edwards N. , Goldman R. .
Source: Journal Of Proteome Research, 2012-03-02 00:00:00.0; 11(3), p. 1728-40.
PMID: 22239659
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Delineating Diseases By Ims-ms Profiling Of Serum N-linked Glycans
Authors: Isailovic D. , Plasencia M.D. , Gaye M.M. , Stokes S.T. , Kurulugama R.T. , Pungpapong V. , Zhang M. , Kyselova Z. , Goldman R. , Mechref Y. , et al. .
Source: Journal Of Proteome Research, 2012-02-03 00:00:00.0; 11(2), p. 576-85.
PMID: 22148953
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Ms/ms Library Facilitated Mrm Quantification Of Native Peptides Prepared By Denaturing Ultrafiltration
Authors: Lenco J. , Lan R. , Edwards N. , Goldman R. .
Source: Proteome Science, 2012; 10(1), p. 7.
PMID: 22304756
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Proteome-wide Analysis Of Single-nucleotide Variations In The N-glycosylation Sequon Of Human Genes
Authors: Mazumder R. , Morampudi K.S. , Motwani M. , Vasudevan S. , Goldman R. .
Source: Plos One, 2012; 7(5), p. e36212.
PMID: 22586465
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Urinary Estrogen Metabolites And Prostate Cancer Risk: A Pilot Study
Authors: Kosti O. , Xu X. , Veenstra T.D. , Hsing A.W. , Chu L.W. , Goldman L. , Bebu I. , Collins S. , Dritschilo A. , Lynch J.H. , et al. .
Source: The Prostate, 2011 Apr; 71(5), p. 507-16.
PMID: 20886539
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Peptides In Low Molecular Weight Fraction Of Serum Associated With Hepatocellular Carcinoma
Authors: An Y. , Bekesova S. , Edwards N. , Goldman R. .
Source: Disease Markers, 2010; 29(1), p. 11-20.
PMID: 20826913
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Detection of hepatocellular carcinoma using glycomic analysis.
Authors: Goldman R. , Ressom H.W. , Varghese R.S. , Goldman L. , Bascug G. , Loffredo C.A. , Abdel-Hamid M. , Gouda I. , Ezzat S. , Kyselova Z. , et al. .
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2009-03-01 00:00:00.0; 15(5), p. 1808-13.
EPub date: 2009-03-01 00:00:00.0.
PMID: 19223512
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