Detection of Hepatocellular Carcinoma Using Glycomic Analysis

Goldman, Radoslav; Ressom, Habtom W.; Varghese, Rency S.; Goldman, Lenka; Bascug, Gregory; Loffredo, Christopher A.; Abdel‐Hamid, Mohamed; Gouda, Iman; Ezzat, Sameera; Kyseľová, Zuzana; Mechref, Yehia; Novotný, Miloš V.

doi:10.1158/1078-0432.ccr-07-5261

Cited by 131 publications

(162 citation statements)

References 37 publications

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“…N-Glycans were detached with PNGaseF (New England Biolabs) overnight at 37°C, reduced with ammonium-borane complex (Sigma-Aldrich), and permethylated as described previously (9,32). MALDI-TOF MS/MS spectra were acquired on a 4800 mass analyzer (AB Sciex) equipped with an Nd:YAG 355-nm laser.…”

Section: Methodsmentioning

confidence: 99%

Site-specific Glycoforms of Haptoglobin in Liver Cirrhosis and Hepatocellular Carcinoma

Pompach

Brnakova

Šanda

et al. 2013

Molecular & Cellular Proteomics

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109

176

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Haptoglobin is a liver-secreted glycoprotein with four Nglycosylation sites. Its glycosylation was reported to change in several cancer diseases, which prompted us to examine site-specific glycoforms of haptoglobin in liver cirrhosis and hepatocellular carcinoma. To this end, we have used two-dimensional separation composed of hydrophilic interaction and nano-reverse phase chromatography coupled to QTOF mass spectrometry of the enriched glycopeptides. Our results show increased fucosylation of haptoglobin in liver disease with up to six fucoses associated with specific glycoforms of one glycopeptide. Structural analysis using exoglycosidase treatment and MALDI-MS/MS of detached permethylated glycans led to the identification of Lewis Y-type structures observed particularly in the pooled hepatocellular carcinoma sample. To confirm the increase of the Lewis Y structures observed by LC-MS, we have used immunoaffinity detection with Lewis Y-specific antibodies.

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Section: Methodsmentioning

confidence: 99%

Site-specific Glycoforms of Haptoglobin in Liver Cirrhosis and Hepatocellular Carcinoma

Pompach

Brnakova

Šanda

et al. 2013

Molecular & Cellular Proteomics

Self Cite

109

176

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“…Perhaps the most widely used profiling methods are normal phase HPLC of fluorescently labeled glycans (14,15) and MALDI/TOF mass spectrometric screening of permethylated glycans (16). Chromatographic resolution of the fluorescently labeled complex glycan mixtures can be somewhat limited, although MALDI/TOF screening has lower quantitative accuracy, but both methods have provided good evidence for quantitative shifts in the distribution of protein-associated N-glycans in cancer diseases (17,18). Optimized LC-MS/MS analysis of glycans and even glycopeptides allows improved resolution of isomers and further supports the presence of disease-related protein glycoforms that could impact protein function and disease progression (19 -21).…”

mentioning

confidence: 99%

Quantitative Liquid Chromatography-Mass Spectrometry-Multiple Reaction Monitoring (LC-MS-MRM) Analysis of Site-specific Glycoforms of Haptoglobin in Liver Disease

Šanda¹,

Pompach²,

Brnakova³

et al. 2013

Molecular & Cellular Proteomics

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112

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N-Glycosylation is a common modification that controls protein folding and multiple functions of mature glycoproteins (1). This co-translational process is controlled by the activity of glycosyltransferases and glycosidases localized in the endoplasmic reticulum and Golgi compartments (2), and its importance increases with complexity of the organism (3, 4). Changes in the abundance and microheterogeneity of glycosylation have been associated with several diseases, including cancer. For example, increased core fucosylation, branching, and terminal sialylation of proteins were associated with carcinogenesis in multiple publications (5-7). In this study, we focus on the quantitative monitoring of changes in N-glycosylation of haptoglobin (Hp) 1 in patients with liver disease. Quantitative changes in protein glycosylation have been analyzed on the level of enzymatically detached N-glycans and on the level of glycopeptides, but the analyses of detached glycans are better developed. Almost all reported quantifications are based on relative quantities partly because quantitative standards are not readily accessible and because changes in relative distributions are considered more important than absolute quantities of the analytes. The only paper we are aware of reporting HPLC-based absolute quantification of glycans used a standard isolated from hen egg yolk for analysis of enzymatically detached N-glycans in rheumatoid arthritis (8).Multiple workflows for relative (semi)quantitative analysis of detached N-glycans, using various analytical techniques, were described (9 -13). Perhaps the most widely used profiling methods are normal phase HPLC of fluorescently labeled glycans (14, 15) and MALDI/TOF mass spectrometric screening of permethylated glycans (16). Chromatographic resolution of the fluorescently labeled complex glycan mixtures can be somewhat limited, although MALDI/TOF screening has From the

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“…Serum glycomic studies to discover novel glycan cancer biomarkers have been highlighted (Adamczyk et al 2012 ). Numerous glycan tumor marker candidates for various cancers, including liver (Kaji et al 2013 ;Kamiyama et al 2013 ;Wu et al 2012 ;Tang et al 2010 ;Goldman et al 2009 ;Comunale et al 2009 ;Tanabe et al 2008 ;Ressom et al 2008 ), ovary (Biskup et al 2013 ;Hua et al 2013 ;Alley et al 2012 ;Abbott et al 2010 ;Leiserowitz et al 2008 ), pancreas (Li et al 2009 ;Okuyama et al 2006), breast (de Leoz et al 2011Alley et al 2010 ;Zeng et al 2010 ;Storr et al 2008 ;Abd Hamid et al 2008 ;Kyselova et al 2008 ;Kirmiz et al 2007 ), prostate , lung (Arnold et al 2011 ), colorectum (Zhao et al 2012 ), bile duct (Silsirivanit et al 2011 ), and esophagus ) cancers, have been reported. Most of these glycomic analyses have been carried out by newly developed high-throughput platform technologies, such as mass spectrometry-based methods and lectin-based methods, which have enabled the effi cient analysis of large cohorts of samples.…”

Section: Glycomic Studies On Serum Of Cancer Patientsmentioning

confidence: 99%

Glycomic Analysis of Cancer

Miyamoto

2014

Sugar Chains

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Remarkable alterations in oligosaccharide structures are associated with many human diseases, including cancers. Numerous clinicopathological and biochemical studies have suggested the involvement of aberrant glycosylation in cancer malignancy, such as metastasis and invasion. Furthermore, altered carbohydrate determinants, including tumor-associated carbohydrate antigens such as SLe a (CA19-9), have been utilized as useful tumor markers for the diagnosis of cancer. Cancer glycomic analysis (i.e., precise and comprehensive analysis of altered oligosaccharides in cancer tissues and sera) is a widely used tool for (1) investigating the involvement of glycosylation in cancer malignancy and (2) discovering novel carbohydrate tumor marker candidates. Comprehensive clinico-glycomic studies of glycosphingolipids of colorectal cancers have revealed specifi c alterations related to malignant transformation, as well as characteristic alterations associated with clinical features. Glycomic analyses of colorectal cancers and pancreatic cancers revealed the presence of two kinds of novel fucogangliosides, sialylated type1H (Lewis-negative specifi c antigen) and sialylated type2H, both of which are isomers of sialyl Le x and sialyl Le a . The accumulation of free oligosaccharides in human cancers has been elucidated. Free Neu5Ac-containing complex-type N -glycans accumulated in pancreatic cancers. In addition to these free oligosaccharides, free KDN-containing complex-type N -glycans accumulated in prostate cancers. N -linked and O -linked glycans have also been targets for cancer glycomics. In particular, extensive studies of serum glycomic analyses have been performed to fi nd novel glycan cancer biomarker utilizing newly developed high-throughput platform technologies. It is anticipated that these cancer glycomic studies will lead to the discovery of glycan biomarker or therapy targets for cancers.

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Detection of Hepatocellular Carcinoma Using Glycomic Analysis

Cited by 131 publications

References 37 publications

Site-specific Glycoforms of Haptoglobin in Liver Cirrhosis and Hepatocellular Carcinoma

Site-specific Glycoforms of Haptoglobin in Liver Cirrhosis and Hepatocellular Carcinoma

Quantitative Liquid Chromatography-Mass Spectrometry-Multiple Reaction Monitoring (LC-MS-MRM) Analysis of Site-specific Glycoforms of Haptoglobin in Liver Disease

Glycomic Analysis of Cancer

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