= Emerging. More than 5 years before clinical availability. (26.62%)
= Expected to be clinically available in 1 to 4 years. (38.91%)
= Clinically available now. (34.47%)
MSACL 2020 US : Hall

MSACL 2020 US Abstract

Topic: Lipidomics

Podium Presentation in the Ether on Wednesday at 14:20 (Chair: Michael Chen)

Lipid Profiling and Imaging Predict Proliferation Status of Hepatocellular Carcinoma

Zoe Hall (Presenter)
Imperial College London

Presenter Bio(s): Zoe Hall is a Lecturer in Lipid Metabolism and Signalling, in the Faculty of Medicine (Division of Systems Biology) at Imperial College London.

Authors: Zoe Hall (1, 2), Evelina Charidemou (2), Davide Chiarugi (2), Fiona Oakley (3), Matthew Hoare (4), Michele Vacca (2), Julian Griffin (1, 2)
(1) Imperial College London, United Kingdom (2) University of Cambridge, Cambridge, United Kingdom, (3) Newcastle University, Newcastle upon Tyne, United Kingdom, (4) CRUK Cambridge Institute, Cambridge, United Kingdom


INTRODUCTION: Hepatocytes undergo profound metabolic rewiring when primed to proliferate during compensatory regeneration. Aberrant hepatocyte proliferation in chronic liver disease is also a driving cause of hepatocellular carcinoma (HCC), one of the leading causes of cancer-related deaths world-wide. Characterising the metabolic remodelling that hepatocytes undergo during compensatory regeneration and in HCC is thus crucial to identify metabolic pathways that relate to cell proliferation in general and, more specifically, to HCC growth.

METHODS: In order to capture the metabolic signature of proliferating hepatocytes, we applied state-of-the-art systems biology approaches to models of liver regeneration, pharmacologically- and genetically-activated cell proliferation, and both mouse and human HCC. We integrated metabolomics, lipidomics and transcriptomics data, performed metabolic flux analysis and used mass spectrometry imaging (MSI) to study metabolic remodelling in proliferation and cancer.

RESULTS: An increase in monounsaturated fatty acid (MUFA)-containing phosphatidylcholine (PC) was measured by lipidomics in all the models, and confirmed by MSI in cancer. We integrated data from lipidomics, metabolomics and transcriptomics to link these changes in lipid content to specific pathways. These included increased lipogenesis, fatty acyl desaturation and de novo synthesis of PC, and decreased beta-oxidation. We confirm this altered lipid signature in human HCC and show a strong positive correlation of MUFA-PC with proliferation markers, cell cycle control and other known genetic markers of HCC.

DISCUSSION: Since hepatic MUFA-PC was closely correlated with proliferation and other markers of HCC, these lipids have the potential to become new prognostic markers and enable improved patient stratification. Finally, our study suggests that these lipid remodelling mechanisms are not necessarily cancer-specific but more broadly associated with hepatocyte proliferation. This has important implications to better understand the role of lipid metabolism in the pathophysiological events linking NASH-cirrhosis to HCC but also in terms of personalised medicine.

CONCLUSION: Overall, we demonstrate that specific lipid metabolic pathways are coherently altered when hepatocytes switch to proliferation. These represent a source of targets for the development of new therapeutic strategies and prognostic biomarkers of HCC.

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