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1H-NMR-based metabolomics of tumor tissue for the metabolic characterization of rat hepatocellular carcinoma formation and metastasis

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Tumor Biology

Abstract

The high mortality figures for hepatocellular carcinoma (HCC) are mostly due to high recurrence and metastasis rates. However, the metabolic characteristics of HCC metastasis have not been studied extensively. In this study, we attempted to elucidate the metabolite profile of HCC formation and metastasis through proton nuclear magnetic resonance (1H-NMR)-based metabolomics. We first established a hepatocellular carcinoma with lung metastasis (HLM) rat model by exposure to diethylnitrosamine. Fifteen rats were then divided into three groups based on pathologic changes: HCC, HLM, and controls. The metabolite profiles of extracts from tumor tissue were obtained using high-resolution 1H-NMR. One-way ANOVA was used to compare the metabolite levels among the three groups. Multivariate statistical analysis (specifically, unsupervised principal components analysis and supervised partial least squares discriminant analysis (PLS-DA)) were used for HCC and HLM metabolite profiling and data interpretation. PLS-DA models could discern HCC or HLM rats from normal (control) rats. Tumor tissue from HLM showed changes in glucose, lactate, choline, lipids, and some amino acids such as glycine. The results of this pilot study suggest that alterations in glycolysis and the metabolism of glycine and choline occur during HCC invasion and metastasis.

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Acknowledgements

We thank Dr. Xianzhong Yan (National Center of Biomedical Analysis, Beijing, China) for his valuable technical assistance. This research was funded through a grant from the National Natural Science Foundation of the People’s Republic of China, No. 30571818.

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Authors and Affiliations

  1. Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, No. 157, West 5th Road, Xi’an, 710004, Shaanxi, China

    Juan Wang, Shu Zhang, Zongfang Li, Rongrui Liang, Zhongwei Liu & Rui Zhou

  2. Department of Pathology, Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, 710004, Shaanxi, China

    Jun Yang

  3. Key Laboratory of Environment and Genes Related to Diseases of the Education Ministry, School of Medicine, Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, China

    Chen Huang

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  1. Juan Wang
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  4. Jun Yang
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Correspondence to Zongfang Li.

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Juan Wang and Shu Zhang contribute to this paper equally as the first authors.

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Wang, J., Zhang, S., Li, Z. et al. 1H-NMR-based metabolomics of tumor tissue for the metabolic characterization of rat hepatocellular carcinoma formation and metastasis. Tumor Biol. 32, 223–231 (2011). https://doi.org/10.1007/s13277-010-0116-7

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  • DOI: https://doi.org/10.1007/s13277-010-0116-7

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