A serum metabolomic investigation on hepatocellular carcinoma patients by chemical derivatization followed by gas chromatography/mass spectrometry

Xue, Ruyi; Lin, Zhenxin; Deng, Chunhui; Dong, Ling; Liu, Taotao; Wang, Jiyao; Shen, Xizhong

doi:10.1002/rcm.3708

Cited by 86 publications

(82 citation statements)

References 59 publications

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“…The acquired GC/MS data were analyzed by stepwise discriminant analysis and a support vector machine. 38 The metabolites including butanoic acid, ethanimidic acid, glycerol, L-isoleucine, L-valine, aminomalonic acid, D-erythrose, hexadecanoic acid, octadecanoic acid, and 9,12-octadecadienoic acid in combination with each other gave the strongest segregation between the two groups. By applying these variables, it provided a diagnostic model that could well discriminate between HCC patients and normal subjects, and appears to be a useful tool in the area of HCC diagnosis.…”

Section: Biomarkers and Metabolomics Studies On Hccmentioning

confidence: 95%

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: 95%

Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma

2013

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“…Nontarget metabolomics approaches have also been used to search for new biomarkers and to explore the mechanism of carcinogenesis in hepatic diseases (11)(12)(13)(14)(15)(16)(17)(18)(19)(20). According to these stud-ies, several circulation metabolites have been reported to be predictors for HCC, such as hexanal, 1-octen-3-ol, octane (18), and a combination of multimetabolites (21). Soga et al found that serum ␥-glutamyl dipeptides can be used as biomarkers for discriminating different liver diseases (22).…”

Section: Hepatocellular Carcinoma (Hcc)mentioning

confidence: 99%

Metabolomics Study of Stepwise Hepatocarcinogenesis From the Model Rats to Patients: Potential Biomarkers Effective for Small Hepatocellular Carcinoma Diagnosis

Tan

Yin

Tang

et al. 2012

Molecular & Cellular Proteomics

137

126

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The aim of this study is to find the potential biomarkers from the rat hepatocellular carcinoma (HCC) disease model by using a non-target metabolomics method, and test their usefulness in early human HCC diagnosis. The serum metabolic profiling of the diethylnitrosamine-induced rat HCC model, which presents a stepwise histopathological progression that is similar to human HCC, was performed using liquid chromatography-mass spectrometry. Multivariate data analysis methods were utilized to identify the potential biomarkers. Three metabolites, taurocholic acid, lysophosphoethanolamine 16:0, and lysophosphatidylcholine 22:5, were defined as "marker metabolites," which can be used to distinguish the different stages of chemical hepatocarcinogenesis. These metabolites represented the abnormal metabolism during the progress of hepatocarcinogenesis, which could also be found in patients. To test their diagnosis potential 412 sera from 262 patients with HCC, 76 patients with cirrhosis and 74 patients with chronic hepatitis B were collected and studied, it was found that 3 marker metabolites were effective for the discrimination of small liver tumor (solitary nodules of less than 2 cm in diameter) patients, achieved a sensitivity of 80.5% and a specificity of 80.1%,which is better than those of ␣-fetoprotein (53 and 64%, respectively). Moreover, they were also effective for the discrimination of all HCCs and chronic liver disease patients, which could achieve a sensitivity of 87.5% and a specificity of 72.3%, better than those of ␣-fetoprotein (61.2 and 64%). These results indicate metabolomics method has

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“…The mixture was left to react for 1 h in a microwave oven at 90 °C. After incubation, the samples were again vortex-mixed for 1 min and prepared for GC-MS analysis (Xue et al, 2008).…”

Section: Specimen Processingmentioning

confidence: 99%

“…The mass spectrometer was operated in electron impact (EI) mode (70 eV) and mass was acquired from m/z 45 to m/z 500 at a mass accuracy of 0.1 atomic mass units. The acceleration voltage was turned on after a solvent delay of 6 min (Xue et al, 2008).…”

Section: Gc-ms Analysismentioning

confidence: 99%

Response to weaning and dietary l-glutamine supplementation: metabolomic analysis in piglets by gas chromatography/mass spectrometry

Xiao

Hong

et al. 2012

J. Zhejiang Univ. Sci. B

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A novel metabolomic method based on gas chromatography/mass spectrometry (GC-MS) was applied to determine the metabolites in the serum of piglets in response to weaning and dietary L-glutamine (Gln) supplementation. Thirty-six 21-d-old piglets were randomly assigned into three groups. One group continued to suckle from the sows (suckling group), whereas the other two groups were weaned and their diets were supplemented with 1% (w/w) Gln or isonitrogenous L-alanine, respectively, representing Gln group or control group. Serum samples were collected to characterize metabolites after a 7-d treatment. Results showed that twenty metabolites were down-regulated significantly (P<0.05) in control piglets compared with suckling ones. These data demonstrated that early weaning causes a wide range of metabolic changes across arginine and proline metabolism, aminosugar and nucleotide metabolism, galactose metabolism, glycerophospholipid metabolism, biosynthesis of unsaturated fatty acid, and fatty acid metabolism. Dietary Gln supplementation increased the levels of creatinine, D-xylose, 2-hydroxybutyric acid, palmitelaidic acid, and α-L-galactofuranose (P<0.05) in early weaned piglets, and were involved in the arginine and proline metabolism, carbohydrate metabolism, and fatty acid metabolism. A leave-one-out cross-validation of random forest analysis indicated that creatinine was the most important metabolite among the three groups. Notably, the concentration of creatinine in control piglets was decreased (P=0.00001) compared to the suckling piglets, and increased (P=0.0003) in Gln-supplemented piglets. A correlation network for weaned and suckling piglets revealed that early weaning changed the metabolic pathways, leading to the abnormality of carbohydrate metabolism, amino acid metabolism, and lipid metabolism, which could be partially improved by dietary Gln supplementation. These findings provide fresh insight into the complex metabolic changes in response to early weaning and dietary Gln supplementation in piglets.

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A serum metabolomic investigation on hepatocellular carcinoma patients by chemical derivatization followed by gas chromatography/mass spectrometry

Cited by 86 publications

References 59 publications

Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma

Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma

Metabolomics Study of Stepwise Hepatocarcinogenesis From the Model Rats to Patients: Potential Biomarkers Effective for Small Hepatocellular Carcinoma Diagnosis

Response to weaning and dietary l-glutamine supplementation: metabolomic analysis in piglets by gas chromatography/mass spectrometry

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