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Open AccessArticle

Phospholipids are A Potentially Important Source of Tissue Biomarkers for Hepatocellular Carcinoma: Results of a Pilot Study Involving Targeted Metabolomics

1
The Queen’s Medical Center, Honolulu, HI 96813, USA
2
University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI 96813, USA
3
Departments of Medicine and Surgery, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA
*
Author to whom correspondence should be addressed.
Diagnostics 2019, 9(4), 167; https://doi.org/10.3390/diagnostics9040167
Received: 22 September 2019 / Revised: 16 October 2019 / Accepted: 24 October 2019 / Published: 29 October 2019
(This article belongs to the Collection Biomarkers in Medicine)
Background: Hepatocellular carcinoma (HCC) pathogenesis involves the alteration of multiple liver-specific metabolic pathways. We systematically profiled cancer- and liver-related classes of metabolites in HCC and adjacent liver tissues and applied supervised machine learning to compare their potential yield for HCC biomarkers. Methods: Tumor and corresponding liver tissue samples were profiled as follows: Bile acids by ultra-performance liquid chromatography (LC) coupled to tandem mass spectrometry (MS), phospholipids by LC-MS/MS, and other small molecules including free fatty acids by gas chromatography—time of flight MS. The overall classification performance of metabolomic signatures derived by support vector machine (SVM) and random forests machine learning algorithms was then compared across classes of metabolite. Results: For each metabolite class, there was a plateau in classification performance with signatures of 10 metabolites. Phospholipid signatures consistently showed the highest discrimination for HCC followed by signatures derived from small molecules, free fatty acids, and bile acids with area under the receiver operating characteristic curve (AUC) values of 0.963, 0.934, 0.895, 0.695, respectively, for SVM-generated signatures comprised of 10 metabolites. Similar classification performance patterns were observed with signatures derived by random forests. Conclusion: Membrane phospholipids are a promising source of tissue biomarkers for discriminating between HCC tumor and liver tissue. View Full-Text
Keywords: hepatocellular carcinoma; metabolomics; diagnosis; phospholipids; machine learning; molecular imaging; positron emission tomography hepatocellular carcinoma; metabolomics; diagnosis; phospholipids; machine learning; molecular imaging; positron emission tomography
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Evangelista, E.B.; Kwee, S.A.; Sato, M.M.; Wang, L.; Rettenmeier, C.; Xie, G.; Jia, W.; Wong, L.L. Phospholipids are A Potentially Important Source of Tissue Biomarkers for Hepatocellular Carcinoma: Results of a Pilot Study Involving Targeted Metabolomics. Diagnostics 2019, 9, 167.

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