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Metabolomics

, 15:156 | Cite as

Clinical and metabolomics analysis of hepatocellular carcinoma patients with diabetes mellitus

  • Hongping XiaEmail author
  • Jianxiang Chen
  • Karthik Sekar
  • Ming Shi
  • Tian Xie
  • Kam M. HuiEmail author
Original Article

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.

Keywords

Diabetes Hepatocellular carcinoma Metabolites Principal component analysis Metabolomics 

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

Notes

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.”.

Author 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.

Compliance with ethical standards

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.

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 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 CommissionNanjing Medical UniversityNanjingChina
  2. 2.Laboratory of Cancer Genomics, Division of Cellular and Molecular ResearchNational Cancer CentreSingaporeSingapore
  3. 3.Holistic Integrative Pharmacy Institutes (HIPI)Hangzhou Normal UniversityHangzhouChina
  4. 4.Department of Hepatobiliary Oncology, Cancer CenterSun Yat-sen UniversityGuangzhouChina
  5. 5.Institute of Molecular and Cell Biology, A*STARSingaporeSingapore
  6. 6.Department of Biochemistry, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
  7. 7.Cancer and Stem Cell Biology ProgramDuke-NUS Medical SchoolSingaporeSingapore

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