Serum metabolomics reveals γ-glutamyl dipeptides as biomarkers for discrimination among different forms of liver disease

Soga, Tomoyoshi; Sugimoto, Masahiro; Honma, Masashi; Mori, Masayo; Igarashi, Kaori; Kashikura, Kasumi; Ikeda, Satsuki; Hirayama, Akiyoshi; Yamamoto, Takehito; Yoshida, Haruhiko; Otsuka, Motoyuki; Tsuji, Shoji; Yatomi, Yutaka; Sakuragawa, Tadayuki; Watanabe, Hisayoshi; Nihei, Kouei; Saito, Takafumi; Kawata, Sumio; Suzuki, Hiroshi; Tomita, Masaru; Suematsu, Makoto

doi:10.1016/j.jhep.2011.01.031

Cited by 216 publications

(160 citation statements)

References 33 publications

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“…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). In our previous metabolomics studies on HCC based on the metabolic profiling of serum and urine (14,19), we found that the levels of several metabolites, such as sphingosines in blood and carnitines in urine, were statistically significantly different between the patients and controls.…”

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

138

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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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

138

126

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“…Recenly, γ-glutamyl dipeptides have also been reported as biomarkers to discriminate six different CLD and HCC [15]. And also, some important serum metabolites have been found altered in HCC and CIR involved in lipid metabolism, increased protein degradation, perturbations of the tricarboxylic acid (TCA) cycle [16].…”

Section: Introductionmentioning

confidence: 99%

Serum metabolomics reveals the deregulation of fatty acids metabolism in hepatocellular carcinoma and chronic liver diseases

et al. 2012

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Patients with chronic liver diseases (CLD) including chronic hepatitis B and hepatic cirrhosis (CIR) are the major high-risk population of hepatocellular carcinoma (HCC). The differential diagnosis between CLD and HCC is a challenge. This work aims to study the related metabolic deregulations in HCC and CLD to promote the discovery of the differential metabolites for distinguishing the different liver diseases. Serum metabolic profiling analysis from patients with CLD and HCC was performed using a liquid chromatography-mass spectrometry system. The acquired large amount of metabolic information was processed with the random forest-recursive feature elimination method to discover important metabolic changes. It was found that long-chain acylcarnitines accumulated, whereas free carnitine, medium and short-chain acylcarnitines decreased with the severity of the non-malignant liver diseases, accompanied with corresponding alterations of enzyme activities. However, the general changing extent was smaller in HCC than in CIR, possibly due to the special energy-consumption mechanism of tumor cells. These observations may help to understand the mechanism of HCC occurrence and progression on the metabolic level and provide information for the identification of early and differential metabolic markers for HCC.

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“…Current screening methodologies for liver cancer in at-risk patients rely on measuring the serum level of a-fetoprotein (AFP), a biomarker, as well as ultrasound imaging. 3 AFP's sensitivity is very limited since many other liver diseases can result in a very high blood level of AFP similar to that observed in HCC. 4,5 Therefore, more sensitive markers of disease are needed, particularly for the early detection of HCC disease, and highly sensitive and specific biomarkers such as primary indicators are relatively more useful.…”

mentioning

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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Serum metabolomics reveals γ-glutamyl dipeptides as biomarkers for discrimination among different forms of liver disease

Cited by 216 publications

References 33 publications

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

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

Serum metabolomics reveals the deregulation of fatty acids metabolism in hepatocellular carcinoma and chronic liver diseases

Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma

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