High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance Spectroscopy of Paired Clinical Liver Tissue Samples from Hepatocellular Cancer and Surrounding Region

Author:

Fernandes Wendy M.12,Harris Nicola12ORCID,Zamalloa Ane3,Adofina Lissette3,Srinivasan Parthi3,Menon Krishna3,Heaton Nigel3,Miquel Rosa4ORCID,Zen Yoh4,Kelly Geoff5,Jarvis James A.6ORCID,Oregioni Alain5,Chokshi Shilpa12,Riva Antonio12ORCID,Cox I. Jane12ORCID

Affiliation:

1. The Roger Williams Institute of Hepatology, Foundation for Liver Research, 111 Coldharbour Lane, London SE5 9NT, UK

2. Faculty of Life Sciences & Medicine, King’s College London, London WC2R 2LS, UK

3. Institute of Liver Studies, King’s College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK

4. Liver Histopathology Laboratory, Institute of Liver Studies, King’s College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK

5. MRC Biomedical NMR Centre, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK

6. Randall Centre for Cell & Molecular Biophysics and Centre for Biomolecular Spectroscopy, King’s College London, London SE1 1UL, UK

Abstract

The global burden of liver cancer is increasing. Timely diagnosis is important for optimising the limited available treatment options. Understanding the metabolic consequences of hepatocellular carcinoma (HCC) may lead to more effective treatment options. We aimed to document metabolite differences between HCC and matched surrounding tissues of varying aetiology, obtained at the time of liver resection, and to interpret metabolite changes with clinical findings. High-resolution magic angle spinning nuclear magnetic resonance (HRMAS-NMR) spectroscopy analyses of N = 10 paired HCC and surrounding non-tumour liver tissue samples were undertaken. There were marked HRMAS-NMR differences in lipid levels in HCC tissue compared to matched surrounding tissue and more subtle changes in low-molecular-weight metabolites, particularly when adjusting for patient-specific variability. Differences in lipid-CH3, lipid-CH2, formate, and acetate levels were of particular interest. The obvious differences in lipid content highlight the intricate interplay between metabolic adaptations and cancer cell survival in the complex microenvironment of liver cancer. Differences in formate and acetate might relate to bacterial metabolites. Therefore, documentation of metabolites in HCC tissue according to histology findings in patients is of interest for personalised medicine approaches and for tailoring targeted treatment strategies.

Funder

Roger Williams Institute of Hepatology, Foundation for Liver Research

MRC Biomedical NMR Centre at The Francis Crick Institute

Wellcome Trust and British Heart Foundation

Publisher

MDPI AG

Reference56 articles.

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