Abstract
Introduction
Arachidonic acid (AA)-derived prostaglandins recently have been implicated in pathogenesis of hepatocellular carcinoma (HCC). However, current understanding of omega-6-derived oxylipins that promote this disease remains limited, particularly on oxylipins derived from linoleic acid (LA).
Objective
Hepatitis B virus (HBV) infection is a major risk factor for HCC in Asia, we thus quantified AA- and LA-derived oxylipins and the two parent polyunsaturated fatty acids in HBV-related HCC patients to assist in understanding of the molecular pathogenesis of HCC.
Methods
Serum samples from 40 HBV-related HCC patients and 23 age-sex matched healthy controls were analyzed using liquid chromatography tandem mass spectrometry.
Results
LA, LA-derived oxylipins such as 9-hydroxyoctadecadienoic acid (9-HODE), 13-HODE, 9,10-dihydroxyoctadecenoic acid (9,10-DiHOME), and 12,13-DiHOME, as well as AA-derived oxylipins such as 5,6-dihydroxyeicosatrienoic acid (5,6-DiHETrE), 11,12-DiHETrE, and 14,15-DiHETrE, were significantly elevated in HCC patients compared to healthy controls. Of these, LA, 13-HODE, and 9-HODE showed good potential in differentiating HCC patients from healthy controls (AUC >0.8).
Conclusion
The study demonstrated LA- and AA-derived oxylipins via the lipoxygenase and cytochrome P450 pathways appeared to be most involved in the pathogenesis of HBV-related HCC.
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Acknowledgements
We thank all participants for their invaluable contribution to the study.
Funding
This study was partially supported by the Grant of Natural Science Fund of The Science and Technology Commission of Shanghai, China (12ZR1404300), Science and Technology Commission of Shanghai Municipality (16,411,954,300), NUS secondment Funds to CNO (706-000-005-133) and NUS Environmental Research Institute (NERI) (608-000-007-731). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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All procedures performed in studies 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.
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Informed consent was obtained from all individual participants included in the study.
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Yonghai Lu and Jinling Fang have contributed equally to this work.
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Lu, Y., Fang, J., Ong, C.N. et al. Targeted analysis of omega-6-derived oxylipins and parent polyunsaturated fatty acids in serum of hepatitis B virus-related hepatocellular carcinoma patients. Metabolomics 13, 6 (2017). https://doi.org/10.1007/s11306-016-1148-9
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DOI: https://doi.org/10.1007/s11306-016-1148-9