Dataset Information

Site-specific glycoforms of haptoglobin in liver cirrhosis and hepatocellular carcinoma.

ABSTRACT: Haptoglobin is a liver-secreted glycoprotein with four N-glycosylation 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. The presence of multiply fucosylated Lewis Y glycoforms of haptoglobin in the disease context could have important functional implications.

SUBMITTER: Pompach P

PROVIDER: S-EPMC3650339 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Site-specific glycoforms of haptoglobin in liver cirrhosis and hepatocellular carcinoma.

Pompach Petr P Brnakova Zuzana Z Sanda Miloslav M Wu Jing J Edwards Nathan N Goldman Radoslav R

Molecular & cellular proteomics : MCP 20130206 5

Haptoglobin is a liver-secreted glycoprotein with four N-glycosylation 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 ...[more]

PMID: 23389049

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Project description:ImportanceCurrent recommendations for patients with cirrhosis are to undergo surveillance for hepatocellular carcinoma (HCC) with ultrasonography (US) every 6 months. However, the sensitivity of US screening to detect early-stage HCC is suboptimal. Magnetic resonance imaging (MRI) with liver-specific contrast may detect additional HCCs missed by US in high-risk patients with cirrhosis.ObjectiveTo compare the HCC detection rate of US and MRI in patients with cirrhosis who are at high risk for HCC.Design, setting, and participantsA prospective surveillance study of 407 patients with cirrhosis and an estimated annual risk of HCC greater than 5% who underwent 1 to 3 biannual screening examinations with paired US and liver-specific contrast-enhanced MRI at a tertiary care hospital between November 2011 and August 2014. All patients were followed-up with dynamic computed tomography (CT) at 6 months after the study. The confirmation of HCC was based on the results of histologic examination and/or typical CT images of HCC.Main outcomes and measuresHCC detection rates and false-positive findings of US vs MRI.ResultsA total of 407 eligible patients received 1100 screenings with paired US and MRI. Hepatocellular carcinomas were diagnosed in 43 patients: 1 detected by US only, 26 by MRI only, 11 by both, and 5 were missed by both. The HCC detection rate of MRI was 86.0% (37/43), significantly higher than the 27.9% (12/43) of US (P < .001). Magnetic resonance imaging showed a significantly lower rate of false-positive findings than US (3.0% vs 5.6%; P = .004). Of the 43 patients with HCC, 32 (74.4%) had very early-stage HCC (a single nodule <2 cm), and 29 (67.4%) received curative treatments. The 3-year survival rate of the patients with HCC (86.0%) was not inferior to those without HCC (94.2%; hazard ratio, 2.26; 95% CI, 0.92-5.56; P = .08).Conclusions and relevanceIn patients with cirrhosis at high-risk of HCC, screening that used MRI with liver-specific contrast resulted in a higher HCC detection rate and lower false-positive findings compared with US. With MRI screening, most of the cancers detected were at very early stage, which was associated with a high chance of curative treatments and favorable survival of patients. Whether surveillance with MRI would reduce mortality from HCC in high-risk patients requires further investigation.Trial registrationclinicaltrials.gov Identifier: NCT01446666.

Dataset Information

Site-specific glycoforms of haptoglobin in liver cirrhosis and hepatocellular carcinoma.

Publications

Site-specific glycoforms of haptoglobin in liver cirrhosis and hepatocellular carcinoma.

Similar Datasets

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