Metabolomic profiling of human urine in hepatocellular carcinoma patients using gas chromatography/mass spectrometry

Wu, Hao; Xue, Ruyi; Dong, Ling; Liu, Taotao; Deng, Chunhui; Zeng, Hao; Shen, Xizhong

doi:10.1016/j.aca.2009.06.033

Cited by 154 publications

(103 citation statements)

References 37 publications

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“…In a recent work, the metabolomic method was used to investigate the urinary metabolic difference between HCC male patients and normal male subjects. 35 The urinary endogenous metabolome was assayed using chemical derivatization followed by GC/MS. After GC/MS analysis, 103 metabolites were detected, of which 18 metabolites were shown to be significantly different between the HCC and control groups.…”

Section: Biomarkers and Metabolomics Studies On Hccmentioning

confidence: 99%

Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma

2013

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Hepatocellular carcinoma (HCC) is the commonest primary hepatic malignancy and the third most common cause of cancer-related death worldwide. Incidence remains highest in the developing world and is steadily increasing across the developed world. Current diagnostic modalities, of ultrasound and a-fetoprotein, are expensive and lack sensitivity in tumor detection. Because of its asymptomatic nature, HCC is usually diagnosed at late and advanced stages, for which there are no effective therapies. Thus, biomarkers for early detection and molecular targets for treating HCC are urgently needed. Emerging highthroughput metabolomics technologies have been widely applied, aiming at the discovery of candidate biomarkers for cancer staging, prediction of recurrence and prognosis, and treatment selection. Metabolic profiles, which are affected by many physiological and pathological processes, may provide further insight into the metabolic consequences of this severe liver disease. Small-molecule metabolites have an important role in biological systems and represent attractive candidates to understand HCC phenotypes. The power of metabolomics allows an unparalleled opportunity to query the molecular mechanisms of HCC. This technique-driven review aims to demystify the metabolomics pathway, while also illustrating the potential of this technique, with recent examples of its application in

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Section: Biomarkers and Metabolomics Studies On Hccmentioning

confidence: 99%

Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma

2013

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“…Recently metabolomic study of HCC has been performed by high resolution magic-angle spinning 1 H nuclear magnetic resonance spectroscopy (19) and a panel of 13 differential tissue metabolites, including alanine, leucine and glucose were identified. Several serum and urine metabolites as potential markers in a small number of HCC patients (n ϭ 20) were identified by gas chromatography mass spectrometry (GC-MS, LC-MS) (20,21), including nucleosides, butanoic acid, ethanimidic acid, glycerol, isoleucine, valine, aminomalonic acid, glycine, tyrosine, threonine, etc.…”

Section: Hepatocelluar Carcinoma (Hcc)mentioning

confidence: 99%

Serum and Urine Metabolite Profiling Reveals Potential Biomarkers of Human Hepatocellular Carcinoma

Chen

Xie

Wang

et al. 2011

Molecular & Cellular Proteomics

264

118

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Hepatocellular carcinoma (HCC) is a common malignancy in the world with high morbidity and mortality rate. Identification of novel biomarkers in HCC remains impeded primarily because of the heterogeneity of the disease in clinical presentations as well as the pathophysiological variations derived from underlying conditions such as cirrhosis and steatohepatitis. The aim of this study is to search for potential metabolite biomarkers of human HCC using serum and urine metabolomics approach. Sera and urine samples were collected from patients with HCC (n ‫؍‬ 82), benign liver tumor patients (n ‫؍‬ 24), and healthy controls (n ‫؍‬ 71). Metabolite profiling was performed by gas chromatography time-of-flight mass spectrometry and ultra performance liquid chromatography-quadrupole time of flight mass spectrometry in conjunction with univariate and multivariate statistical analyses. Forty three serum metabolites and 31 urinary metabolites were identified in HCC patients involving several key metabolic pathways such as bile acids, free fatty acids, glycolysis, urea cycle, and methionine metabolism. Differentially expressed metabolites in HCC subjects, such as bile acids, histidine, and inosine are of great statistical significance and high fold changes, which warrant further validation as potential biomarkers for HCC. However, alterations of several bile acids seem to be affected by the condition of liver cirrhosis and hepatitis. Quantitative measurement and comparison of seven bile acids among benign liver tumor patients with liver cirrhosis and hepatitis, HCC patients with liver cirrhosis and hepatitis, HCC patients without liver cirrhosis and hepatitis, and healthy controls revealed that the abnormal levels of glycochenodeoxycholic acid, glycocholic acid, taurocholic acid, and chenodeoxycholic acid are associated with liver cirrhosis and hepatitis. HCC patients with alpha fetoprotein values lower than 20 ng/ml was successfully differentiated from healthy controls with an accuracy of 100% using a panel of metabolite markers. Our work shows that metabolomic profiling approach is a promising screening tool for the diagnosis and stratification of HCC patients.Molecular & Cellular Proteomics 10: 10.1074/mcp.M110.004945, 1-13, 2011. Hepatocelluar carcinoma (HCC)1 is the fifth most common cancer (1) and the third leading cause of cancer-related death (2) with a five-year survival rate of less than 7% (3). The morbidity of HCC in Southeast Asia and sub-Saharan Africa is greater than 20 cases per 100,000 population, whereas in North America and Western Europe is much lower, less than 5 per 100,000 population (4). However, a dramatically increasing incidence of HCC in the world, especially in the United States has been reported in recent years, primarily because of chronic alcohol use and chronic hepatitis C infection (5). Diabetic and metabolic diseases of the liver have been known to contribute to an increased incidence of HCC in recent years (6, 7). Despite significant progress in cancer diagnosis and treatment, the morbidity...

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“…This has led to the identification of various metabolically impaired pathways in serum and urine (7)(8)(9)(10). However, these data were obtained in small sample-sized cohorts of patients and important clinical information was lacking, such as the stage of liver cancer and the cause and degree of severity of the underlying liver disease, which can induce specific and serious serum metabolic disturbances (11).…”

Section: Introductionmentioning

confidence: 99%

Identification of Serum Proton NMR Metabolomic Fingerprints Associated with Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis

Nahon

Amathieu

Triba

et al. 2012

Clinical Cancer Research

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Purpose: Metabolomics depicts metabolic changes in biologic systems using a multiparametric analysis technique. This study assessed the metabolomic profiles of serum, obtained by proton nuclear magnetic resonance (NMR) spectroscopy, from cirrhotic patients with and without hepatocellular carcinoma (HCC).Experimental Design: The study included 154 consecutive patients with compensated biopsy-proven alcoholic cirrhosis. Among these, 93 had cirrhosis without HCC, 28 had biopsy-proven HCC within the Milan criteria and were eligible for curative treatment (small HCC), and 33 had HCC outside the Milan criteria (large HCC). Proton spectra were acquired at 500 MHz. An orthogonal partial latent structure [orthogonal projection to latent structure (OPLS)] analysis model was built to discriminate large HCC spectra from cirrhotic spectra. Small HCC spectra were secondarily projected using previously built OPLS discriminant components.Results: The OPLS model showed discrimination between cirrhotic and large HCC spectra. Metabolites that significantly increased with large HCC were glutamate, acetate, and N-acetyl glycoproteins, whereas metabolites that correlated with cirrhosis were lipids and glutamine. Projection of small HCC samples into the OPLS model showed a heterogeneous distribution between large HCC and cirrhotic samples. Small HCC patients with metabolomic profile similar to those of large HCC group had higher incidences of recurrence or death during follow-up.Conclusions: Serum NMR-based metabolomics identified metabolic fingerprints that could be specific to large HCC in cirrhotic livers. From a metabolomic standpoint, some patients with small HCC, who are eligible for curative treatments, seem to behave as patients with advanced cancerous disease. It would be useful to further prospectively investigate these patients to define a subgroup with a worse prognosis. Clin Cancer Res; 18(24); 6714-22. Ó2012 AACR.

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Metabolomic profiling of human urine in hepatocellular carcinoma patients using gas chromatography/mass spectrometry

Cited by 154 publications

References 37 publications

Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma

Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma

Serum and Urine Metabolite Profiling Reveals Potential Biomarkers of Human Hepatocellular Carcinoma

Identification of Serum Proton NMR Metabolomic Fingerprints Associated with Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis

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