Clinical and metabolomics analysis of hepatocellular carcinoma patients with diabetes mellitus
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.
The study aimed to identify clinical and metabolomics differences of HCC from patients with/without diabetes using comprehensive global metabolomics analysis.
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.
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.
Metabolic profiling identifies distinct dysregulated metabolites in HCC patients with/without diabetes.
KeywordsDiabetes Hepatocellular carcinoma Metabolites Principal component analysis Metabolomics
Principal component analysis
Chronic hepatitis B
Hepatitis B virus
Gas chromatography coupled to mass spectrometry
Type 2 diabetes mellitus
Ultra performance liquid chromatography–tandem mass spectrometer
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.”.
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.
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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