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Clinical utility of high-throughput glycome analysis in patients with pancreatic cancer

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

Most of the glycan changes reported in cancers were based on the examinations of a small number of patients or particular proteins. The aim of this study was to determine the changes of the serum N-glycan profile comprehensively in a large number of pancreatic cancer patients and investigate its clinical utility.

Methods

Glycan levels in the serum of 92 pancreatic cancer patients and 243 healthy volunteers (HLT) were examined by comprehensive quantitative high-throughput glycome analysis and were compared with clinical parameters.

Results

Out of 66 glycans detected, 15 were differentially expressed in pancreatic cancer, and 10 out of the 15 glycans were significantly up-regulated in cases with distant metastasis. There was a clear increase in overall expression of serum glycans, especially highly-branched glycans with fucose moieties, in pancreatic cancer. Among these 15 glycans, a tri-antennary complex type glycan (m/z 3195) showed the highest area under the receiver operating characteristic curve (AUROC = 0.799) for the diagnosis of pancreatic cancer. The ratio of pairs of glycans on the same path of the biosynthesis pathway (m/z 3195/1914) was found to be significantly higher in pancreatic cancer than in HLT (median = 1.11 and 0.41, respectively; p < 0.0001, AUROC = 0.831). For this pair ratio, the hazard ratio for survival (2.60, 95 % CI = 1.44–4.79) was higher than that of any single glycan and 1-year survival of patients with a high and low ratio was 36.9 and 69.2 %, respectively, (p = 0.001).

Conclusions

Comprehensive glycome analysis can be used to know the presence of pancreatic cancer, distant metastasis, and patient prognosis, simultaneously.

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Acknowledgments

This work was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (KAKENHI 23590976), partly by a grant for “Development of Systems and Technology for Advanced Measurement and Analysis (SENTAN)” and “The Matching Program for Innovations in Future Drug Discovery and Medical Care” from the Japan Science and Technology Agency (JST) and the Ministry of Education, Culture, Science, and Technology, Japan.

Conflict of interest

Kazuhiro Nouso received a research grant from a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science and a research grant from the Japan Science and Technology Agency (JST). Kazuhiro Nouso belongs to a donation-funded department (Department of Molecular Hepatology, funded by MSD). Shin-Ichiro Nishimura received a research grant from the Japan Science and Technology Agency (JST) and the Ministry of Education, Culture, Science, and Technology, Japan; Shin-Ichiro Nishimura is a Chief Scientific Office of Medical Chemistry Pharmaceuticals LLC. Maho Amano is a Director of Technology at Medical Chemistry Pharmaceuticals LLC. Taku Nakahara is a Director of Ezose Science Inc. Hideki Onishi belongs to a donation-funded department (Department of Molecular Hepatology, funded by MSD). Fusao Ikeda belongs to a donation-funded department (Department of Molecular Hepatology, funded by MSD).

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Authors and Affiliations

  1. Department of Molecular Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, Okayama, 700-8558, Japan

    Kazuhiro Nouso, Hideki Onishi & Fusao Ikeda

  2. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan

    Kazuhiro Nouso, Koji Miyahara, Yuki Morimoto, Hironari Kato, Koichiro Tsutsumi, Takeshi Tomoda, Naoki Yamamoto, Shinichiro Nakamura, Sayo Kobayashi, Kenji Kuwaki, Hiroaki Hagihara, Hideki Onishi, Yasuhiro Miyake, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki & Kazuhide Yamamoto

  3. Field of Drug Discovery Research, Faculty of Advanced Life Science and Graduate School of Life Science, Hokkaido University, Sapporo, Japan

    Maho Amano & Shin-Ichiro Nishimura

  4. Medical Chemistry Pharmaceuticals LLC, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    Maho Amano & Shin-Ichiro Nishimura

  5. Department of Biostatistics, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    Yoichi M. Ito

  6. Ezose Sciences Incorporation, New Jersey, USA

    Taku Nakahara

Authors
  1. Kazuhiro Nouso
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  2. Maho Amano
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  3. Yoichi M. Ito
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  5. Yuki Morimoto
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  8. Takeshi Tomoda
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  9. Naoki Yamamoto
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  13. Hiroaki Hagihara
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  14. Hideki Onishi
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  15. Yasuhiro Miyake
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  16. Fusao Ikeda
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  17. Hidenori Shiraha
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  18. Akinobu Takaki
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  19. Taku Nakahara
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  20. Shin-Ichiro Nishimura
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  21. Kazuhide Yamamoto
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Corresponding author

Correspondence to Kazuhiro Nouso.

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Nouso, K., Amano, M., Ito, Y.M. et al. Clinical utility of high-throughput glycome analysis in patients with pancreatic cancer. J Gastroenterol 48, 1171–1179 (2013). https://doi.org/10.1007/s00535-012-0732-7

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  • DOI: https://doi.org/10.1007/s00535-012-0732-7

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