Discovery of serotransferrin glycoforms: Novel markers for diagnosis of liver periductal fibrosis and prediction of cholangiocarcinoma

Wassana Jamnongkan, Carlito B. Lebrilla, Mariana Barboza, Anchalee Techasen, Watcharin Loilome, Paiboon Sithithaworn, Narong Khuntikeo, Chawalit Pairojkul, Nittaya Chamadol, Raynoo Thanan, Puangrat Yongvanit

Research output: Contribution to journalArticle

Abstract

Cholangiocarcinoma (CCA) caused by chronic liver fluke infection is a major public health problem in Northeast Thailand. Identification of CCA risk groups is urgently needed for the control of CCA in this region. Periductal fibrosis (PDF) induced by chronic inflammation of bile ducts is known as a pre-neoplastic lesion of CCA. We aimed to identify the serum CCA and PDF biomarkers using mass spectrometry (UPLC-ESI-QqQ) with multiple reaction mode (MRM) analysis. Here, serum levels of serotransferrin glycoforms at the glycopeptide level were measured in the sera of CCA (n = 100), PDF (n = 50), and healthy control (n = 100) subjects. The results indicated that serotransferrin peptide levels were generally the same between the control and PDF groups, whereas CCA patients had reduced levels. Moreover, 56 serotransferrin glycoforms were detected, with nine increased in CCA compared to control subjects. Among them, the serum levels of four glycoforms were increased in PDF and CCA patients compared to control subjects. In particular, highly sialylated multi-branched glycans of serotransferrin serum were significantly correlated with poor prognosis and tumor stage in CCA patients. Taken together, these glycoforms could be used as risk biomarkers and prognosis and diagnosis markers of CCA.

Original languageEnglish (US)
Article number538
JournalBiomolecules
Volume9
Issue number10
DOIs
StatePublished - Oct 2019

Fingerprint

Cholangiocarcinoma
Transferrin
Liver Cirrhosis
Liver
Biomarkers
Fibrosis
Glycopeptides
Serum
Public health
Medical problems
Ducts
Mass spectrometry
Polysaccharides
Tumors
Peptides
Fasciola hepatica
Electrospray Ionization Mass Spectrometry
Thailand
Bile Ducts
Public Health

Keywords

  • Biomarkers
  • Cholangiocarcinoma
  • Glycobiology
  • Liver fluke
  • Mass spectrometry
  • Periductal fibrosis
  • Serotransferrin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Discovery of serotransferrin glycoforms : Novel markers for diagnosis of liver periductal fibrosis and prediction of cholangiocarcinoma. / Jamnongkan, Wassana; Lebrilla, Carlito B.; Barboza, Mariana; Techasen, Anchalee; Loilome, Watcharin; Sithithaworn, Paiboon; Khuntikeo, Narong; Pairojkul, Chawalit; Chamadol, Nittaya; Thanan, Raynoo; Yongvanit, Puangrat.

In: Biomolecules, Vol. 9, No. 10, 538, 10.2019.

Research output: Contribution to journalArticle

Jamnongkan, W, Lebrilla, CB, Barboza, M, Techasen, A, Loilome, W, Sithithaworn, P, Khuntikeo, N, Pairojkul, C, Chamadol, N, Thanan, R & Yongvanit, P 2019, 'Discovery of serotransferrin glycoforms: Novel markers for diagnosis of liver periductal fibrosis and prediction of cholangiocarcinoma', Biomolecules, vol. 9, no. 10, 538. https://doi.org/10.3390/biom9100538
Jamnongkan, Wassana ; Lebrilla, Carlito B. ; Barboza, Mariana ; Techasen, Anchalee ; Loilome, Watcharin ; Sithithaworn, Paiboon ; Khuntikeo, Narong ; Pairojkul, Chawalit ; Chamadol, Nittaya ; Thanan, Raynoo ; Yongvanit, Puangrat. / Discovery of serotransferrin glycoforms : Novel markers for diagnosis of liver periductal fibrosis and prediction of cholangiocarcinoma. In: Biomolecules. 2019 ; Vol. 9, No. 10.
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AU - Techasen, Anchalee

AU - Loilome, Watcharin

AU - Sithithaworn, Paiboon

AU - Khuntikeo, Narong

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AU - Thanan, Raynoo

AU - Yongvanit, Puangrat

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AB - Cholangiocarcinoma (CCA) caused by chronic liver fluke infection is a major public health problem in Northeast Thailand. Identification of CCA risk groups is urgently needed for the control of CCA in this region. Periductal fibrosis (PDF) induced by chronic inflammation of bile ducts is known as a pre-neoplastic lesion of CCA. We aimed to identify the serum CCA and PDF biomarkers using mass spectrometry (UPLC-ESI-QqQ) with multiple reaction mode (MRM) analysis. Here, serum levels of serotransferrin glycoforms at the glycopeptide level were measured in the sera of CCA (n = 100), PDF (n = 50), and healthy control (n = 100) subjects. The results indicated that serotransferrin peptide levels were generally the same between the control and PDF groups, whereas CCA patients had reduced levels. Moreover, 56 serotransferrin glycoforms were detected, with nine increased in CCA compared to control subjects. Among them, the serum levels of four glycoforms were increased in PDF and CCA patients compared to control subjects. In particular, highly sialylated multi-branched glycans of serotransferrin serum were significantly correlated with poor prognosis and tumor stage in CCA patients. Taken together, these glycoforms could be used as risk biomarkers and prognosis and diagnosis markers of CCA.

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