Metabolomics and eicosanoid analysis identified serum biomarkers for distinguishing hepatocellular carcinoma from hepatitis B virus-related cirrhosis

Gong, Zhi; Zhao, Weijie; Zhang, Jianbing; Wu, Xi; Hu, Jing; Yin, Guo Chang; Xu, Yong

doi:10.18632/oncotarget.19173

Cited by 46 publications

(30 citation statements)

References 46 publications

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“…Multiple metabolomic studies on HBV+ and HCV+ patients have been reported. For HBV, the studies mostly sought biomarkers of the development of cirrhosis or HCC [ 24 , 46 , 47 , 48 , 49 ] or biomarkers simply of HBV infection itself [ 10 , 28 ]. Similar studies have been reported in the case of HCV for serum biomarkers of progression to HCC [ 21 , 22 , 23 ] and for hepatic fibrosis [ 17 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

Robust Regression Analysis of GCMS Data Reveals Differential Rewiring of Metabolic Networks in Hepatitis B and C Patients

et al. 2017

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About one in 15 of the world’s population is chronically infected with either hepatitis virus B (HBV) or C (HCV), with enormous public health consequences. The metabolic alterations caused by these infections have never been directly compared and contrasted. We investigated groups of HBV-positive, HCV-positive, and uninfected healthy controls using gas chromatography-mass spectrometry analyses of their plasma and urine. A robust regression analysis of the metabolite data was conducted to reveal correlations between metabolite pairs. Ten metabolite correlations appeared for HBV plasma and urine, with 18 for HCV plasma and urine, none of which were present in the controls. Metabolic perturbation networks were constructed, which permitted a differential view of the HBV- and HCV-infected liver. HBV hepatitis was consistent with enhanced glucose uptake, glycolysis, and pentose phosphate pathway metabolism, the latter using xylitol and producing threonic acid, which may also be imported by glucose transporters. HCV hepatitis was consistent with impaired glucose uptake, glycolysis, and pentose phosphate pathway metabolism, with the tricarboxylic acid pathway fueled by branched-chain amino acids feeding gluconeogenesis and the hepatocellular loss of glucose, which most probably contributed to hyperglycemia. It is concluded that robust regression analyses can uncover metabolic rewiring in disease states.

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Section: Discussionmentioning

confidence: 99%

Robust Regression Analysis of GCMS Data Reveals Differential Rewiring of Metabolic Networks in Hepatitis B and C Patients

et al. 2017

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“…As expected, the HCC group showed a significant increased Alfa fetoprotein (AFP) level compared to CLD patients (p = 0.02), as well as prothrombin time expressed as an international normalized ratio (INR) (p = 0.005) and decreased level of hemoglobin (p = 0.011). 0.311 (2) Alanine transaminase (IU/L) Mean (range) 56 58 27 0.878 (a) 0.003 (2) Aspartate transaminase (IU/L) Mean (range) 65 48 26 (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) 0.115 (a) 0.001 (2) Hemoglobin (g/L) Mean (range)…”

Section: Characteristics Of Subjectsmentioning

confidence: 99%

“…Gas chromatography/mass spectrometry (GC/MS) provided good coverage of primary metabolism in HCC ranging from energy metabolism [14] to glycolysis, TCA metabolites, purines, and lipids [30,31]. Specifically, GC/MS revealed alterations in amino acids, sugars, fatty acids, and other macromolecules in biofluids of HCC patients [22,25,[32][33][34][35][36]. However, none of these earlier studies combined analyses of both tissues and biofluids for detailing the pathogenesis of HCC in patients.…”

Section: Introductionmentioning

confidence: 99%

Sugar Alcohols Have a Key Role in Pathogenesis of Chronic Liver Disease and Hepatocellular Carcinoma in Whole Blood and Liver Tissues

Ismail

Fiehn

Elfert

et al. 2020

Cancers

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The major risk factors for hepatocellular carcinoma (HCC) are hepatitis C and B viral infections that proceed to Chronic Liver Disease (CLD). Yet, the early diagnosis and treatment of HCC are challenging because the pathogenesis of HCC is not fully defined. To better understand the onset and development of HCC, untargeted GC-TOF MS metabolomics data were acquired from resected human HCC tissues and their paired non-tumor hepatic tissues (n = 46). Blood samples of the same HCC subjects (n = 23) were compared to CLD (n = 15) and healthy control (n = 15) blood samples. The participants were recruited from the National Liver Institute in Egypt. The GC-TOF MS data yielded 194 structurally annotated compounds. The most strikingly significant alteration was found for the class of sugar alcohols that were up-regulated in blood of HCC patients compared to CLD subjects (p < 2.4 × 10−12) and CLD compared to healthy controls (p = 4.1 × 10−7). In HCC tissues, sugar alcohols were the most significant (p < 1 × 10−6) class differentiating resected HCC tissues from non-malignant hepatic tissues for all HCC patients. Alteration of sugar alcohol levels in liver tissues also defined early-stage HCC from their paired non-malignant hepatic tissues (p = 2.7 × 10−6). In blood, sugar alcohols differentiated HCC from CLD subjects with an ROC-curve of 0.875 compared to 0.685 for the classic HCC biomarker alpha-fetoprotein. Blood sugar alcohol levels steadily increased from healthy controls to CLD to early stages of HCC and finally, to late-stage HCC patients. The increase in sugar alcohol levels indicates a role of aldo-keto reductases in the pathogenesis of HCC, possibly opening novel diagnostic and therapeutic options after in-depth validation.

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“…HBV infection decrease ATP levels in hepatocytes . Several other metabolites from mitochondria, in particular, citrate and succinate, are implicated in the pathological processes of viral hepatitis and cirrhosis . Given the complexity, whether it is a sequential or causal relationship between mitochondrial alteration and hepatitis remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Mitochondria in the biology, pathogenesis, and treatment of hepatitis virus infections

Zhang

et al. 2019

Reviews in Medical Virology

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Summary Hepatitis virus infections affect a large proportion of the global population. The host responds rapidly to viral infection by orchestrating a variety of cellular machineries, in particular, the mitochondrial compartment. Mitochondria actively regulate viral infections through modulation of the cellular innate immunity and reprogramming of metabolism. In turn, hepatitis viruses are able to modulate the morphodynamics and functions of mitochondria, but the mode of actions are distinct with respect to different types of hepatitis viruses. The resulting mutual interactions between viruses and mitochondria partially explain the clinical presentation of viral hepatitis, influence the response to antiviral treatment, and offer rational avenues for novel therapy. In this review, we aim to consider in depth the multifaceted interactions of mitochondria with hepatitis virus infections and emphasize the implications for understanding pathogenesis and advancing therapeutic development.

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Metabolomics and eicosanoid analysis identified serum biomarkers for distinguishing hepatocellular carcinoma from hepatitis B virus-related cirrhosis

Cited by 46 publications

References 46 publications

Robust Regression Analysis of GCMS Data Reveals Differential Rewiring of Metabolic Networks in Hepatitis B and C Patients

Robust Regression Analysis of GCMS Data Reveals Differential Rewiring of Metabolic Networks in Hepatitis B and C Patients

Sugar Alcohols Have a Key Role in Pathogenesis of Chronic Liver Disease and Hepatocellular Carcinoma in Whole Blood and Liver Tissues

Mitochondria in the biology, pathogenesis, and treatment of hepatitis virus infections

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