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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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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DOI: https://doi.org/10.1007/s00216-012-5782-4