Differential metabonomic profiles of primary hepatocellular carcinoma tumors from alcoholic liver disease, HBV-infected, and HCV-infected cirrhotic patients.

Ding Cao,Junhua Gong,Jinzheng Li,Menghao Wang,Can Cai,Jianping Gong,Mingxin Ye

doi:10.18632/oncotarget.18397

Abstract

Our objective was to comparatively profile the metabolite composition of primary hepatocellular carcinoma (HCC) tumors from alcoholic liver disease (ALD), hepatitis B virus (HBV)-infected, and hepatitis C virus (HCV)-infected cirrhotic patients. Primary HCC tumors were collected from ALD, HBV-infected, and HCV-infected cirrhotic patients (n=20 each). High-resolution magic-angle spinning proton nuclear magnetic resonance spectroscopy and metabonomic data analysis were performed to compare HCC tumors from the three groups. Sensitivity analyses were performed to determine the effects of diabetes, high body mass index, and smoking status. Metabonomic pathway analyses were conducted to identify dysregulated pathways. Three metabolites were significantly differentiated between ALD and HBV-infected patients, which were distinguishable by changes in ketone body, glycerolipid, and phenylalanine metabolism. Five metabolites were significantly differentiated between ALD and HCV-infected patients, which were distinguishable by changes in ketone body, alanine/aspartate/glutamate, and phenylalanine metabolism. Six metabolites were significantly differentiated between HBV-infected and HCV-infected patients, which were distinguishable by changes in ketone body, tyrosine, and alanine/aspartate/glutamate metabolism. In conclusion, this is the first study to demonstrate that the metabolic phenotypes of primary HCC tumors vary significantly across ALD, HBV-infected, and HCV-infected cirrhotic patients.

Highlights

Hepatocellular carcinoma (HCC) remains a key research area due to hepatocellular carcinoma (HCC)’s high mortality rates and complicated pathogenesis [1]
This is the first study to demonstrate that the metabolic phenotypes of primary HCC tumors vary significantly across alcoholic liver disease (ALD), HBVinfected, and hepatitis C virus (HCV)-infected cirrhotic patients
Previous metabolomic studies on HCC tumors have demonstrated upregulation of glycolysis, gluconeogenesis, and β-oxidation coupled with TCA cycle downregulation [10, 14], this is the first study to demonstrate that the metabolic phenotypes of primary HCC tumors vary significantly across ALD, HBVinfected, and HCV-infected cirrhotic patients

Summary

Introduction

Hepatocellular carcinoma (HCC) remains a key research area due to HCC’s high mortality rates and complicated pathogenesis [1]. Chronic HBV infection, chronic HCV infection, and alcohol abuse have all been acknowledged to contribute to HCC www.impactjournals.com/oncotarget development, the mechanisms underlying the pathogenesis of HCC in each of these three clinical scenarios remains unclear. The introduction of metabonomics -- the quantitative analysis of the metabolic response of a biological system to external stimuli [7] -- has provided more information on HCC by focusing on the metabolite endproducts that are affected by environmental factors [8]. Blood-based and urinebased metabonomic analyses are easy to perform and can reveal important peripheral pathological changes [9], metabonomic analysis of the actual liver tissue sampled by biopsy or surgery can be useful in identifying the underlying pathogenic changes in HCC tumors in response to external stimuli

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Conclusion