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• Wei, S
• Suryani, Y
• Gowda, G
• Skill, N
• Maluccio, M
• Raftery, D
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• Wei, S
• Suryani, Y
• Gowda, G
• Skill, N
• Maluccio, M
• Raftery, D
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• Wei, S
• Suryani, Y
• Gowda, G
• Skill, N
• Maluccio, M
• Raftery, D

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Metabolites 2012, 2(4), 701-716; doi:10.3390/metabo2040701

Article

Differentiating Hepatocellular Carcinoma from Hepatitis C Using Metabolite Profiling

Siwei Wei ¹ , Yuliana Suryani ¹ , G. A. Nagana Gowda ¹ , Nicholas Skill ² , Mary Maluccio ^2,*  and Daniel Raftery ^1,3,*

¹ Department of Chemistry, Purdue University, 560 Oval Dr., West Lafayette, IN 47907, USA ² Department of Surgery, IU School of Medicine, 550 University Blvd., UH 4601, Indianapolis, IN 46202, USA

* Authors to whom correspondence should be addressed.

Received: 1 August 2012; in revised form: 12 September 2012 / Accepted: 25 September 2012 / Published: 10 October 2012

(This article belongs to the Special Issue Metabolism and Systems Biology)

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Abstract: Hepatocellular carcinoma (HCC) accounts for most liver cancer cases worldwide. Contraction of the hepatitis C virus (HCV) is considered a major risk factor for liver cancer. In order to identify the risk of cancer, metabolic profiling of serum samples from patients with HCC (n=40) and HCV (n=22) was performed by ¹H nuclear magnetic resonance spectroscopy. Multivariate statistical analysis showed a distinct separation of the two patient cohorts, indicating a distinct metabolic difference between HCC and HCV patient groups based on signals from lipids and other individual metabolites. Univariate analysis showed that three metabolites (choline, valine and creatinine) were significantly altered in HCC. A PLS-DA model based on these three metabolites showed a sensitivity of 80%, specificity of 71% and an area under the receiver operating curve of 0.83, outperforming the clinical marker alpha-fetoprotein (AFP). The robustness of the model was tested using Monte-Carlo cross validation (MCCV). This study showed that metabolite profiling could provide an alternative approach for HCC screening in HCV patients, many of whom have high risk for developing liver cancer.

Keywords: hepatocellular carcinoma; heptatitis C; metabolomics; NMR

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