A novel serum metabolomics-based diagnostic approach for colorectal cancer

Shin Nishiumi, Takashi Kobayashi, Atsuki Ikeda, Tomoo Yoshie, Megumi Kibi, Yoshihiro Izumi, Tatsuya Okuno, Nobuhide Hayashi, Seiji Kawano, Tadaomi Takenawa, Takeshi Azuma, Masaru Yoshida

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Background: To improve the quality of life of colorectal cancer patients, it is important to establish new screening methods for early diagnosis of colorectal cancer. Methodology/Principal Findings: We performed serum metabolome analysis using gas-chromatography/mass-spectrometry (GC/MS). First, the accuracy of our GC/MS-based serum metabolomic analytical method was evaluated by calculating the RSD% values of serum levels of various metabolites. Second, the intra-day (morning, daytime, and night) and inter-day (among 3 days) variances of serum metabolite levels were examined. Then, serum metabolite levels were compared between colorectal cancer patients (N = 60; N = 12 for each stage from 0 to 4) and age- and sex-matched healthy volunteers (N = 60) as a training set. The metabolites whose levels displayed significant changes were subjected to multiple logistic regression analysis using the stepwise variable selection method, and a colorectal cancer prediction model was established. The prediction model was composed of 2-hydroxybutyrate, aspartic acid, kynurenine, and cystamine, and its AUC, sensitivity, specificity, and accuracy were 0.9097, 85.0%, 85.0%, and 85.0%, respectively, according to the training set data. In contrast, the sensitivity, specificity, and accuracy of CEA were 35.0%, 96.7%, and 65.8%, respectively, and those of CA19-9 were 16.7%, 100%, and 58.3%, respectively. The validity of the prediction model was confirmed using colorectal cancer patients (N = 59) and healthy volunteers (N = 63) as a validation set. At the validation set, the sensitivity, specificity, and accuracy of the prediction model were 83.1%, 81.0%, and 82.0%, respectively, and these values were almost the same as those obtained with the training set. In addition, the model displayed high sensitivity for detecting stage 0-2 colorectal cancer (82.8%). Conclusions/Significance: Our prediction model established via GC/MS-based serum metabolomic analysis is valuable for early detection of colorectal cancer and has the potential to become a novel screening test for colorectal cancer.

Original languageEnglish
Article numbere40459
JournalPloS one
Volume7
Issue number7
DOIs
Publication statusPublished - Jul 11 2012

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Metabolomics
metabolomics
colorectal neoplasms
Colorectal Neoplasms
Metabolites
Serum
Gas chromatography
Mass spectrometry
prediction
Gas Chromatography-Mass Spectrometry
metabolites
Screening
Early Detection of Cancer
Cystamine
Sensitivity and Specificity
Hydroxybutyrates
volunteers
Kynurenine
Healthy Volunteers
kynurenine

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Nishiumi, S., Kobayashi, T., Ikeda, A., Yoshie, T., Kibi, M., Izumi, Y., ... Yoshida, M. (2012). A novel serum metabolomics-based diagnostic approach for colorectal cancer. PloS one, 7(7), [e40459]. https://doi.org/10.1371/journal.pone.0040459

A novel serum metabolomics-based diagnostic approach for colorectal cancer. / Nishiumi, Shin; Kobayashi, Takashi; Ikeda, Atsuki; Yoshie, Tomoo; Kibi, Megumi; Izumi, Yoshihiro; Okuno, Tatsuya; Hayashi, Nobuhide; Kawano, Seiji; Takenawa, Tadaomi; Azuma, Takeshi; Yoshida, Masaru.

In: PloS one, Vol. 7, No. 7, e40459, 11.07.2012.

Research output: Contribution to journalArticle

Nishiumi, S, Kobayashi, T, Ikeda, A, Yoshie, T, Kibi, M, Izumi, Y, Okuno, T, Hayashi, N, Kawano, S, Takenawa, T, Azuma, T & Yoshida, M 2012, 'A novel serum metabolomics-based diagnostic approach for colorectal cancer', PloS one, vol. 7, no. 7, e40459. https://doi.org/10.1371/journal.pone.0040459
Nishiumi, Shin ; Kobayashi, Takashi ; Ikeda, Atsuki ; Yoshie, Tomoo ; Kibi, Megumi ; Izumi, Yoshihiro ; Okuno, Tatsuya ; Hayashi, Nobuhide ; Kawano, Seiji ; Takenawa, Tadaomi ; Azuma, Takeshi ; Yoshida, Masaru. / A novel serum metabolomics-based diagnostic approach for colorectal cancer. In: PloS one. 2012 ; Vol. 7, No. 7.
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abstract = "Background: To improve the quality of life of colorectal cancer patients, it is important to establish new screening methods for early diagnosis of colorectal cancer. Methodology/Principal Findings: We performed serum metabolome analysis using gas-chromatography/mass-spectrometry (GC/MS). First, the accuracy of our GC/MS-based serum metabolomic analytical method was evaluated by calculating the RSD{\%} values of serum levels of various metabolites. Second, the intra-day (morning, daytime, and night) and inter-day (among 3 days) variances of serum metabolite levels were examined. Then, serum metabolite levels were compared between colorectal cancer patients (N = 60; N = 12 for each stage from 0 to 4) and age- and sex-matched healthy volunteers (N = 60) as a training set. The metabolites whose levels displayed significant changes were subjected to multiple logistic regression analysis using the stepwise variable selection method, and a colorectal cancer prediction model was established. The prediction model was composed of 2-hydroxybutyrate, aspartic acid, kynurenine, and cystamine, and its AUC, sensitivity, specificity, and accuracy were 0.9097, 85.0{\%}, 85.0{\%}, and 85.0{\%}, respectively, according to the training set data. In contrast, the sensitivity, specificity, and accuracy of CEA were 35.0{\%}, 96.7{\%}, and 65.8{\%}, respectively, and those of CA19-9 were 16.7{\%}, 100{\%}, and 58.3{\%}, respectively. The validity of the prediction model was confirmed using colorectal cancer patients (N = 59) and healthy volunteers (N = 63) as a validation set. At the validation set, the sensitivity, specificity, and accuracy of the prediction model were 83.1{\%}, 81.0{\%}, and 82.0{\%}, respectively, and these values were almost the same as those obtained with the training set. In addition, the model displayed high sensitivity for detecting stage 0-2 colorectal cancer (82.8{\%}). Conclusions/Significance: Our prediction model established via GC/MS-based serum metabolomic analysis is valuable for early detection of colorectal cancer and has the potential to become a novel screening test for colorectal cancer.",
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AU - Okuno, Tatsuya

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