Fast and facile analysis of glycosylation and phosphorylation of fibrinogen from human plasma-correlation with liver cancer and liver cirrhosis.
Anal Bioanal Chem
; 410(30): 7965-7977, 2018 Dec.
Article
em En
| MEDLINE
| ID: mdl-30397756
ABSTRACT
Hepatocellular carcinoma (HCC) is one of the deadliest cancers due to its late diagnosis with the main risk factor being liver cirrhosis (LC). Glycan structures from glycoproteins are usually altered in cancer. Blood plasma from 111 healthy and sick donors was analyzed to determine the post-translational modifications (PTM) of intact Aα-, Bß-, and γ-subunits of fibrinogen, a glycoprotein predominantly produced in liver cells. Glycosylation and phosphorylation of the protein species were quantified by liquid chromatography coupled to mass spectrometry to correlate PTMs to pathological cases. Quantities of the PTMs were used for statistical classification by principal component analysis (PCA) and multivariate analysis of variance (MANOVA). As relevant clinical finding, patients with liver disease (HCC and/or LC) were distinguished from individuals without relevant chronic liver disease with 91% sensitivity and 100% specificity. Within the group of patients with liver disease, a robust separation between LC and HCC was not possible. In more detail, the phosphorylation of Aα-subunit is decreased in HCC patients, whereas the monophosphorylated state is significantly increased in LC patients. In terms of glycosylation, the amount of O-glycans in the Aα-subunit is decreased in LC patients, while sialylation and fucosylation of N-type glycans of Bß- and γ-subunits are increased in LC and HCC. Based on PTM of fibrinogen, starting from plasma we can assign the status of an individual as healthy or as liver disease in less than 3 h.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fibrinogênio
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Carcinoma Hepatocelular
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Cirrose Hepática
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Neoplasias Hepáticas
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Anal Bioanal Chem
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Alemanha