Research Paper Advance Articles

Analysis of plasma metabolic profile, characteristics and enzymes in the progression from chronic hepatitis B to hepatocellular carcinoma

Fei-Fei Cai1, *, , Ya-Nan Song1,2, *, , Yi-Yu Lu1, , Yongyu Zhang3, , Yi-Yang Hu4, , Shi-Bing Su1, ,

  • 1 Research Center for Traditional Chinese Medicine Complexity System, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
  • 2 Shanghai Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China
  • 3 Research Center for Traditional Chinese Medicine and System Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
  • 4 Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200203 China
* Equal contribution

Received: March 17, 2020       Accepted: June 4, 2020       Published: July 23, 2020      

https://doi.org/10.18632/aging.103554
How to Cite

Copyright © 2020 Cai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Hepatitis B virus (HBV) infection is an important factor causing hepatocellular carcinoma (HCC). The aim of this study was to investigate the metabolic characteristics and related metabolic enzyme changes during the progression from chronic hepatitis B (CHB) to liver cirrhosis (LC) and, ultimately, to HCC. An untargeted metabolomics assay was performed in plasma from 50 healthy volunteers, 43 CHB patients, 67 LC patients, and 39 HCC patients. A total of 24 differential metabolites (DMs) were identified. Joint pathway analysis suggested striking changes in amino acid metabolism and lipid metabolism from CHB to HCC. The panel of L-serine, creatine and glycine distinguished LC from CHB, and L-serine, cystathionine, creatine and linoleic acid distinguished HCC from LC. Bioinformatic analysis of publicly available data showed that differential metabolite profile-associated enzyme genes, including alanine-glyoxylate aminotransferase-2 (AGXT2), D-amino-acid oxidase (DAO), and cystathionine gamma-lyase (CTH), were downregulated, while bisphosphoglycerate mutase (BPGM), cystathionine-β-synthase (CBS), phosphoserine phosphatase (PSPH) and acyl-CoA thioesterase 7 (ACOT7) were upregulated, in HCC, all of which correlated with a poor prognosis for HCC patients. Our results indicated that serum metabolites and related enzymes are of considerable significance for the diagnosis and prognosis of HCC and can provide a theoretical basis and therapeutic index for future diagnosis and treatment.

Abbreviations

HBV: hepatitis B virus; HCC: hepatocellular carcinoma; CHB: chronic hepatitis B; LC: liver cirrhosis; DM: differential metabolite; NC: normal control; GC-TOFMS: gas chromatography-time of flight-mass spectrometry; GC/MS: gas chromatography mass spectrometry; HBsAg: hepatitis B surface antigen; AST: aspartate transaminase; GGT: gamma-glutamyl transferase; ALP: alkaline phosphatase; TG: triglyceride; TBA: total bile acid; TBIL: total bilirubin; ALB: albumin; PT: prothrombin time; PLS-DA: partial least square discriminant analysis; DMs: differential metabolites; ROC: Receiver operating characteristic; DAO: D-amino-acid oxidase; BPGM: bisphosphoglycerate mutase; CBS: cystathionine-β-synthase; AGXT: alanine-glyoxylate aminotransferase; AGXT2: alanine-glyoxylate aminotransferase-2; CTH: cystathionine gamma-lyase; PGAM1: phosphoglycerate mutase 1; PGAM2: phosphoglycerate mutase 2; PGAM4: phosphoglycerate mutase 4; PSPH: phosphoserine phosphatase; SHMT1: serine hydroxymethyltransferase 1; SHMT2: serine hydroxymethyltransferase 2; ACOT7: acyl-CoA thioesterase 7; LIHC: liver hepatocellular carcinoma; OS: overall survival.