Introduction The liver is a hub of lipid metabolism and previous studies have shown liver disease and hepatocellular carcinoma (HCC) to be associated with altered blood lipid profiles. The primary aim of this study was to examine the lipid profile of HCC in an animal model and to compare findings to changes observed in human populations in an attempt to identify novel lipid tumour biomarkers.
Methods Plasma samples were obtained from a Fisher rat model of HCC (n=7) and healthy controls (n=8). Serum and plasma samples were obtained from patients with HCC and cirrhosis from UK (n=3 and 4) and Nigerian (n=5 and 5) cohorts. All samples were analysed using ultra performance liquid chromatography mass spectrometry (UPLC-MS), optimised using in-house developed dichloromethane lipid extraction protocols. Data were processed using XCMS software followed by multivariate analysis to identify lipids most discriminatory between disease groups.
Results In the rat model, multivariate statistical modelling was robust in classifying animals with HCC from healthy controls. In the human studies, multivariate analyses of lipid profiles were less robust in distinguishing HCC from cirrhosis. Lysophosphatidylcholine (24, 0, 0) (LPC), a major cellular membrane component, was identified as most contributory to all multivariate models.
Conclusion Altered global lipid profiles were robust in discriminating HCC from healthy controls in a Fisher rat model, but less so in parallel human studies. Differences in LPC (24, 0, 0) were present in all studies, which may indicate heightened altered tumour cell turnover as a result of HCC growth. The increased plasma concentrations of LPC in HCC in both species suggests that this molecule may be a robust marker as a lipid tumour biomarker of HCC and requires further validation in lager studies with respect to disease classification and response to therapeutic intervention.
Competing interests None declared.
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