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Analysis of metabolites and metabolic pathways in breast cancer in a Korean prospective cohort: the Korean Cancer Prevention Study-II

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Abstract

Introduction

Since blood is in contact with all tissues in the body and is considered to dynamically reflect the body’s pathophysiological status, serum metabolomics changes are important and have diagnostic value in early cancer detection.

Objectives

In this prospective study, we investigated the application of metabolomics to differentiate subjects with incident breast cancer (BC) from subjects who remained free of cancer during a mean follow-up period of 7 years with the aim of identifying valuable biomarkers for BC.

Methods

Baseline serum samples from 84 female subjects with incident BC (BC group) and 88 cancer-free female subjects (control group) were used. Metabolic alterations associated with BC were investigated via metabolomics analysis of the baseline serum samples using ultra-performance liquid chromatography-linear-trap quadrupole-Orbitrap mass spectrometry.

Results

A total of 57 metabolites were identified through the metabolic analysis. Among them, 20 metabolite levels were significantly higher and 22 metabolite levels were significantly lower in the BC group than in the control group at baseline. Ten metabolic pathways, including amino acid metabolism, arachidonic acid (AA) metabolism, fatty acid metabolism, linoleic acid metabolism, and retinol metabolism, showed significant differences between the BC group and the control group. Logistic regression revealed that the incidence of BC was affected by leucine, AA, prostaglandin (PG)J2, PGE2, and γ-linolenic acid (GLA).

Conclusions

This prospective study showed the clinical relevance of dysregulation of various metabolisms on the incidence of BC. Additionally, leucine, AA, PGJ2, PGE2, and GLA were identified as independent variables affecting the incidence of BC.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Funding

This study was funded by grants from the Korean Health Technology R&D Project, the Ministry of Health & Welfare, Republic of Korea (HI14C2686010116 and HI14C2686); and the Bio-Synergy Research Project of the Ministry of Science ICT through the National Research Foundation, Republic of Korea (NRF-2012M3A9C4048762).

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Authors and Affiliations

  1. Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, South Korea

    Hye Jin Yoo, Minsik Kang & Jong Ho Lee

  2. Research Center for Silver Science, Institute of Symbiotic Life-TECH, Yonsei University, Seoul, South Korea

    Minjoo Kim, Minkyung Kim & Jong Ho Lee

  3. National Leading Research Laboratory of Clinical Nutrigenetics/Nutrigenomics, Department of Food and Nutrition, College of Human Ecology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea

    Minsik Kang & Jong Ho Lee

  4. Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea

    Keum Ji Jung, Se-mi Hwang & Sun Ha Jee

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  1. Hye Jin Yoo
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  2. Minjoo Kim
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  3. Minkyung Kim
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  4. Minsik Kang
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  7. Sun Ha Jee
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  8. Jong Ho Lee
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Contributions

YHJ analyzed and interpreted the data and wrote the manuscript. KM and KM analyzed and interpreted the data. KM conducted experiments. JKJ, HS, and JSH contributed to acquisition of the data. JSH and LJH contributed to the conception and designed the study. LJH interpreted the data and wrote the manuscript. All authors critically revised, read, and approved the final manuscript.

Corresponding author

Correspondence to Jong Ho Lee.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Yoo, H.J., Kim, M., Kim, M. et al. Analysis of metabolites and metabolic pathways in breast cancer in a Korean prospective cohort: the Korean Cancer Prevention Study-II. Metabolomics 14, 85 (2018). https://doi.org/10.1007/s11306-018-1382-4

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