Serum metabolomic profiles for human pancreatic cancer discrimination

Takao Itoi, Masahiro Sugimoto, Junko Umeda, Atsushi Sofuni, Takayoshi Tsuchiya, Shujiro Tsuji, Reina Tanaka, Ryosuke Tonozuka, Mitsuyoshi Honjo, Fuminori Moriyasu, Kazuhiko Kasuya, Yuichi Nagakawa, Yuta Abe, Kimihiro Takano, Shigeyuki Kawachi, Motohide Shimazu, Tomoyoshi Soga, Masaru Tomita, Makoto Sunamura

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Abstract

This study evaluated the clinical use of serum metabolomics to discriminate malignant cancers including pancreatic cancer (PC) from malignant diseases, such as biliary tract cancer (BTC), intraductal papillary mucinous carcinoma (IPMC), and various benign pancreaticobiliary diseases. Capillary electrophoresis–mass spectrometry was used to analyze charged metabolites. We repeatedly analyzed serum samples (n = 41) of different storage durations to identify metabolites showing high quantitative reproducibility, and subsequently analyzed all samples (n = 140). Overall, 189 metabolites were quantified and 66 metabolites had a 20% coefficient of variation and, of these, 24 metabolites showed significant differences among control, benign, and malignant groups (p < 0.05; Steel–Dwass test). Four multiple logistic regression models (MLR) were developed and one MLR model clearly discriminated all disease patients from healthy controls with an area under receiver operating characteristic curve (AUC) of 0.970 (95% confidential interval (CI), 0.946–0.994, p < 0.0001). Another model to discriminate PC from BTC and IPMC yielded AUC = 0.831 (95% CI, 0.650–1.01, p = 0.0020) with higher accuracy compared with tumor markers including carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), pancreatic cancer-associated antigen (DUPAN2) and s-pancreas-1 antigen (SPAN1). Changes in metabolomic profiles might be used to screen for malignant cancers as well as to differentiate between PC and other malignant diseases.

Original languageEnglish
Article number767
JournalInternational Journal of Molecular Sciences
Volume18
Issue number4
DOIs
Publication statusPublished - 2017 Apr 1

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Keywords

  • Biliary tract cancers
  • Capillary electrophoresis mass spectrometry
  • Metabolomics
  • Pancreatic cancer

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Itoi, T., Sugimoto, M., Umeda, J., Sofuni, A., Tsuchiya, T., Tsuji, S., Tanaka, R., Tonozuka, R., Honjo, M., Moriyasu, F., Kasuya, K., Nagakawa, Y., Abe, Y., Takano, K., Kawachi, S., Shimazu, M., Soga, T., Tomita, M., & Sunamura, M. (2017). Serum metabolomic profiles for human pancreatic cancer discrimination. International Journal of Molecular Sciences, 18(4), [767]. https://doi.org/10.3390/ijms18040767