Glycoconjugate Journal

, Volume 35, Issue 5, pp 467–476 | Cite as

Identification of unique glycoisoforms of vitamin D-binding protein and haptoglobin as biomarker candidates in hepatocarcinogenesis of STAM mice

  • Yasunobu Yoshida
  • Jun-ichi Furukawa
  • Shoichi Naito
  • Kenichi Higashino
  • Yoshito Numata
  • Yasuro ShinoharaEmail author
Original Article


Hepatocellular carcinoma (HCC) is the major subtype of primary liver cancer, and is typically diagnosed late in its course. Considering the limitations and the reluctance of patients to undergo a liver biopsy, a reliable, noninvasive diagnostic marker that predicts and assesses the treatment and prognosis of HCC is needed. With recent technological advances of mass spectrometry, glycomics is gathering momentum and holds substantial potential to discover new glycan markers in cancer research. Here, to discover specific glycan markers for the early diagnosis of HCC, we analyzed the glycan profiles of gel-separated serum proteins of progressive liver disease model mice. By focused protein glycomics of 12 gel-separated glycoproteins using sera from the mouse models, we revealed the entire profile of glycans in each major serum protein. We found that the levels of trisialylated triantennary glycans of haptoglobin and vitamin D-binding protein increased significantly as the disease progressed, while the alteration in these protein levels were modest. Furthermore, these glycan increases were not observed in age-matched control mice. In conclusion, our approach has identified specific glycan marker candidates for the early diagnosis of HCC.


Hepatocarcinogenesis Nonalcoholic steatohepatitis Biomarker MALDI-TOF MS Serum glycomics 



Trisialylated triantennary glycans


Diet-induces obesity




Hepatocellular carcinoma


High-fat diet




Nonalcoholic steatohepatitis


Streptozotocin-induced diabetes


Vitamin D-binding protein



Yoshida Y undertook the acquisition and analysis of the data, designed the study, drafted the manuscript and created the figures. Furukawa J and Shinohara Y designed the study, interpreted the data, and critically revised the manuscript. Naito S, Higashino K and Numata Y participated in the study implementation and advised on the study concept. Shinohara Y is responsible for the study conception and the manuscript.


This work was supported in part by the Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

10719_2018_9838_MOESM1_ESM.pdf (452 kb)
ESM 1 (PDF 451 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Yasunobu Yoshida
    • 1
    • 2
  • Jun-ichi Furukawa
    • 3
    • 4
  • Shoichi Naito
    • 1
    • 2
  • Kenichi Higashino
    • 1
    • 5
  • Yoshito Numata
    • 1
    • 6
  • Yasuro Shinohara
    • 3
    • 7
    Email author
  1. 1.Shionogi Innovation Center for Drug DiscoveryShionogi & Co., Ltd.SapporoJapan
  2. 2.Translational Research Unit, Shionogi & Co., Ltd.ToyonakaJapan
  3. 3.Laboratory of Medical and Functional Glycomics, Graduate School of Advanced Life ScienceHokkaido UniversitySapporoJapan
  4. 4.Department of Advanced Clinical Glycobiology, Graduate School of MedicineHokkaido UniversitySapporoJapan
  5. 5.Advanced Chemistry & Informatics, Shionogi & Co., Ltd.ToyonakaJapan
  6. 6.Research Management & Planning Office, Shionogi & Co., Ltd.ToyonakaJapan
  7. 7.Department of PharmacyKinjo Gakuin UniversityNagoyaJapan

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