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Identification of serum biomarkers associated with hepatitis B virus-related hepatocellular carcinoma and liver cirrhosis using mass-spectrometry-based metabolomics

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Abstract

Hepatitis B virus (HBV) infection is a major risk factor for deaths from liver cirrhosis and hepatocellular carcinoma (HCC). With a long-term goal of improving early diagnosis, we aimed to identify specific biomarkers associated with the development of HCC and liver cirrhosis in patients with HBV infection. Serum samples from 46 HBV infected patients with HCC and liver cirrhosis and 24 age–gender matched healthy subjects were profiled by liquid chromatography–mass spectrometry and gas chromatography–mass spectrometry. It was found that fatty acids and long-chain acylcarnitines were significantly elevated in HBV-related HCC patients, whereas most of the carbohydrates, amino acids, short- and medium-chain acylcarnitines, and glycerophospholipids were decreased, when compared to healthy subjects. The up-regulation of fatty acids and long-chain acylcarnitines in HCC was positively correlated with liver cirrhosis state. Logistic regression analysis indicated that palmitoylcarnitine together with arginine was an effective “combined marker” for diagnosing HBV-related HCC with 97.3 % sensitivity and 100 % specificity. Linoleic acid plus glucose was useful for discrimination of liver cirrhosis in HCC patients with 79.2 % sensitivity and 75 % specificity. These findings demonstrate that mass-spectrometry-based metabolomics is a promising tool that could provide special insights into tumor metabolism and identify novel biomarkers for detection of HCC and liver cirrhosis from HBV infected patients.

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Acknowledgments

This study was supported in part by the grant of Natural Science Fund of The Science and Technology Commission of Shanghai, China (No. 12ZR1404300), Singapore Medical Research Council (No. NMRC/1242/2009), the NUS secondment Funds to CNO and the NUS Environmental Research Institute (NERI).

Conflict of Interest

All authors declare that they have no conflict of interest.

Informed Consent

Informed consent was obtained from all individual participants included in the study. All participants voluntarily joined this study, gave written informed consent, and completed a questionnaire that provided demographical information including age, gender, lifestyle factors, and medical family history.

Compliance with Ethical Requirements

All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study protocol was approved by the Ethics Committees of Shanghai Huashan Hospital and National University of Singapore.

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    Authors and Affiliations

    1. Saw Swee Hock School of Public Health, National University of Singapore, Tahir Foundation Building, 12 Science Drive 2, S117549, Singapore, Singapore

      Yonghai Lu, Sin Eng Chia & Choon Nam Ong

    2. Department of Infectious Diseases and Hepatology of Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, China

      Chong Huang, Shengsen Chen, Ning Li, Kangkang Yu, Qingxia Ling, Qi Cheng, Mengqi Zhu & Mingquan Chen

    3. NUS Environmental Research Institute, National University of Singapore, Singapore, Singapore

      Liang Gao & Choon Nam Ong

    4. Key Laboratory of Insect Developmental and Evolutionary Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

      Yong-Jiang Xu

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    1. Yonghai Lu
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    Correspondence to Mingquan Chen or Choon Nam Ong.

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    Yonghai Lu and Chong Huang have contributed equally to this work.

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    Lu, Y., Huang, C., Gao, L. et al. Identification of serum biomarkers associated with hepatitis B virus-related hepatocellular carcinoma and liver cirrhosis using mass-spectrometry-based metabolomics. Metabolomics 11, 1526–1538 (2015). https://doi.org/10.1007/s11306-015-0804-9

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