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Serum metabolomics reveals the deregulation of fatty acids metabolism in hepatocellular carcinoma and chronic liver diseases

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Abstract

Patients with chronic liver diseases (CLD) including chronic hepatitis B and hepatic cirrhosis (CIR) are the major high-risk population of hepatocellular carcinoma (HCC). The differential diagnosis between CLD and HCC is a challenge. This work aims to study the related metabolic deregulations in HCC and CLD to promote the discovery of the differential metabolites for distinguishing the different liver diseases. Serum metabolic profiling analysis from patients with CLD and HCC was performed using a liquid chromatography–mass spectrometry system. The acquired large amount of metabolic information was processed with the random forest–recursive feature elimination method to discover important metabolic changes. It was found that long-chain acylcarnitines accumulated, whereas free carnitine, medium and short-chain acylcarnitines decreased with the severity of the non-malignant liver diseases, accompanied with corresponding alterations of enzyme activities. However, the general changing extent was smaller in HCC than in CIR, possibly due to the special energy-consumption mechanism of tumor cells. These observations may help to understand the mechanism of HCC occurrence and progression on the metabolic level and provide information for the identification of early and differential metabolic markers for HCC.

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Abbreviations

Q-TOF:

Quadrupole time-of-flight

AFP:

α-fetoprotein

ALT:

Alanine transaminase

AST:

Aspartate transaminase

CEA:

Carcinoma embryonic antigen

CHB:

Chronic hepatitis B

CIR:

Hepatic cirrhosis

CLD:

Chronic liver diseases

CN:

Acylcarnitine

CoA:

Coenzyme A

CPT 1:

Carnitine palmitoyl transferase 1

CPT 2:

Carnitine palmitoyl transferase 2

FAO:

Fatty acid oxidation

GCA:

Glycocholic acid

GCDCA:

Chenodeoxycholic acid glycine conjugate

HBsAg:

Hepatitis B surface antigen

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

IDO:

Indoleamine 2,3-dioxygenase

LC-MS:

Liquid chromatography–mass spectrometry system

N:

Healthy controls

OOB:

Out-of-bag

QC:

Quality control

RF:

Random forest

RFE:

Recursive feature elimination

RF-RFE:

Random forest–recursive feature elimination

RRLC:

Rapid-resolution liquid chromatography

SCD:

Stearoyl-CoA desaturase

T2DM:

Type 2 diabetes

TCA:

Tricarboxylic acid

γ-GT:

γ-glutamyl transpeptidase

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Acknowledgments

The study has been supported by the State Key Science and Technology Project for Infectious Diseases (2008ZX10002-017 and 2008ZX10002-019) from State Ministry of Science and Technology of China, and the key foundation (no. 20835006) and the creative research group project (no. 21021004) from National Natural Science Foundation of China.

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Authors and Affiliations

  1. CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China

    Lina Zhou, Peiyuan Yin, Zeming Wu, Shili Chen, Xin Lu & Guowang Xu

  2. School of Computer Science and Technology, Dalian University of Technology, 116024, Dalian, China

    Quancai Wang & Xiaohui Lin

  3. The Sixth People’s Hospital, Dalian, 116001, China

    Wenbin Xing & Yong Zhang

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  1. Lina Zhou
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  2. Quancai Wang
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  9. Xiaohui Lin
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Correspondence to Xiaohui Lin or Guowang Xu.

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Zhou, L., Wang, Q., Yin, P. et al. Serum metabolomics reveals the deregulation of fatty acids metabolism in hepatocellular carcinoma and chronic liver diseases. Anal Bioanal Chem 403, 203–213 (2012). https://doi.org/10.1007/s00216-012-5782-4

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