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Clinical and metabolomics analysis of hepatocellular carcinoma patients with diabetes mellitus

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Abstract

Introduction

Diabetes and cancer are among the most frequent causes of death worldwide. Recent epidemiological findings have indicated a link between diabetes and cancer in several organs, particularly the liver. A number of epidemiological studies have demonstrated that diabetes is an established independent risk factor for hepatocellular carcinoma (HCC). However, the metabolites connecting diabetes and HCC remains less well understood.

Objectives

The study aimed to identify clinical and metabolomics differences of HCC from patients with/without diabetes using comprehensive global metabolomics analysis.

Methods

Metabolite profiling was conducted with the Metabolon platform for 120 human diabetes/non-diabetes HCC tumor/normal tissues. Standard statistical analyses were performed using the Partek Genomics Suite on log-transformed data. Principal component analysis (PCA) was conducted using all and dysregulated metabolites.

Results

We identified a group of metabolites that are differentially expressed in the tumor tissues of diabetes HCC compared to non-diabetes HCC patients. Meanwhile, we also identified a group of metabolites that are differentially expressed in the matched normal liver tissues of diabetes HCC compared to non-diabetes HCC patients. Some metabolites are consistently dysregulated in the tumor or matched normal tissues of HCC with or without diabetes. However, some metabolites, including 2-hydroxystearate, were only overexpressed in the tumor tissues of HCC with diabetes and associated with the glucose level.

Conclusion

Metabolic profiling identifies distinct dysregulated metabolites in HCC patients with/without diabetes.

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Abbreviations

HCC:

Hepatocellular carcinoma

PCA:

Principal component analysis

CHB:

Chronic hepatitis B

HBV:

Hepatitis B virus

GC–MS:

Gas chromatography coupled to mass spectrometry

LTB4:

Leukotriene B4

T2D:

Type 2 diabetes mellitus

UPLC–MS/MS:

Ultra performance liquid chromatography–tandem mass spectrometer

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Acknowledgements

This work was supported by grants from the National Medical Research Council of Singapore, the National Young 1000 Talents Program of China, the Jiangsu Province Education Department, the Jiangsu Province “Innovative and the Entrepreneurial Team” and “Innovative and Entrepreneurial Talent.”.

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Authors and Affiliations

  1. Department of Pathology, School of Basic Medical Sciences & Sir Run Run Hospital & State Key Laboratory of Reproductive Medicine & Key Laboratory of Antibody Technique of National Health Commission, Nanjing Medical University, Nanjing, China

    Hongping Xia & Kam M. Hui

  2. Laboratory of Cancer Genomics, Division of Cellular and Molecular Research, National Cancer Centre, Singapore, Singapore

    Hongping Xia, Karthik Sekar & Kam M. Hui

  3. Holistic Integrative Pharmacy Institutes (HIPI), Hangzhou Normal University, Hangzhou, China

    Jianxiang Chen, Tian Xie & Kam M. Hui

  4. Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, China

    Ming Shi

  5. Institute of Molecular and Cell Biology, A*STAR, Biopolis Drive Proteos, Singapore, Singapore

    Kam M. Hui

  6. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Kam M. Hui

  7. Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore, Singapore

    Kam M. Hui

Authors
  1. Hongping Xia
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  2. Jianxiang Chen
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  3. Karthik Sekar
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  4. Ming Shi
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  5. Tian Xie
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  6. Kam M. Hui
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Contributions

HX and KMH conceived, designed and HX performed the experiments, HX, KS and JC analyzed the data and wrote the manuscript; MS provide the clinical samples and clinical data; KMH and TX sourced funding, KMH supervised the work and contributed to writing the manuscript.

Corresponding authors

Correspondence to Hongping Xia or Kam M. Hui.

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Conflict of interest

The authors declare that they have no conflict of interest concerning the work described.

Ethical approval

This study was approved by the research ethics committee of the Sun Yat-sen University Cancer Center (Guangzhou, China). All tissue samples were collected in accordance with the protocols approved by the Institutional Review Board of the Sun Yat-sen University Cancer Center, and informed consent was obtained from all patients before tissue samples were collected.

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Cite this article

Xia, H., Chen, J., Sekar, K. et al. Clinical and metabolomics analysis of hepatocellular carcinoma patients with diabetes mellitus. Metabolomics 15, 156 (2019). https://doi.org/10.1007/s11306-019-1619-x

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  • DOI: https://doi.org/10.1007/s11306-019-1619-x

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