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High resolution-magic angle spinning (HR-MAS) NMR-based metabolomic fingerprinting of early and recurrent hepatocellular carcinoma

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Abstract

In order to elucidate the metabolite changes associated with hepatocellular carcinoma (HCC) oncogenesis and progression, we compared the profiles obtained by 1D proton HRMAS NMR spectroscopy of 51 needle biopsies (14 primary nodules, 14 recurrent, and 23 paired cirrhotic specimens). The diagnosis of HCC was based on 2 concordant imaging techniques and was confirmed by histology in 20 cases. Spectroscopy was performed using a Bruker AVANCE II 600 spectrometer. One-dimensional proton spectra were acquired using water-suppressed (noesygppr) pulse and spin-echo CPMG sequences. Signals were assigned by BBIOREFCODE and were confirmed by HSQC. Statistics was based on the SIMCA P package. Orthogonal projection to latent structure (OPLS-DA) showed a clear separation between tumor and cirrhosis. This difference was maintained when the analysis of paired samples from primary to recurrent nodules was split. OPLS-DA of primary and recurrent nodules also showed a significant difference. The relationship between metabolite profile and HCC volume was evaluated comparing the spectra obtained in tumors ≤2 cm (n = 15) and in those larger than 2 cm (n = 11). Univariate comparison of the most relevant metabolites showed that: (1) increased choline, TMAO, and decreased saturated fatty acids differentiate HCC from the surrounding tissue; (2) increased lactate and myo-inositol differentiate recurrent from primary HCC; (3) decreased saturated fatty acids characterize large HCC nodules.

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Acknowledgments

The authors wish to thank Dr. F. Benevelli, Dr. A. Minoja and Dr. C. Napoli (Bruker Italy) for suggestions and discussions and Dr. L. Barberini (University of Cagliari) for useful discussions.

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Authors and Affiliations

  1. Institute of Biomolecular Chemistry – National Council of Research – Italy, CNR – National Research Council of Italy, Traversa la Crucca 3, 07040, Sassari, Italy

    Matilde Chessa, Nicola Culeddu & Maria Cristina Porcu

  2. Department of Biomedical Sciences, University of Sassari School of Medicine, Viale San Pietro 12, 07100, Sassari, Italy

    Antonio Solinas

  3. Sardinian Mediterranean Imaging Research Group – (SMIRG) Foundation, Via Stintino 2, 07100, Sassari, Italy

    Giuseppe Virgilio & Vincenzo Migaleddu

  4. Unit of Internal Medicine and Gastroenterology, Department of Medicine, Community Hospital of Nuoro, Via Mannironi, Nuoro, Italy

    Francesco Arcadu

  5. Unit of Internal Medicine, Department of Medicine, Community Hospital of Lanusei, Lanusei, Italy

    Angelo Deplano

  6. Unit of Morbid Anatomy, Department of Pathology, Community Hospital of Nuoro, Via Mannironi, Nuoro, Italy

    Sergio Cossu

  7. Unit of Interventional Echography, Department of Medicine, Community Hospital of Nuoro, Macomer, Nuoro, Italy

    Domenico Scanu

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  1. Antonio Solinas
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  2. Matilde Chessa
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  3. Nicola Culeddu
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  10. Vincenzo Migaleddu
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Correspondence to Nicola Culeddu.

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Solinas, A., Chessa, M., Culeddu, N. et al. High resolution-magic angle spinning (HR-MAS) NMR-based metabolomic fingerprinting of early and recurrent hepatocellular carcinoma. Metabolomics 10, 616–626 (2014). https://doi.org/10.1007/s11306-013-0601-2

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  • DOI: https://doi.org/10.1007/s11306-013-0601-2

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