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

Erin B. Evangelista; Sandi A. Kwee; Miles M. Sato; Lu Wang; Christoph Rettenmeier; Guoxiang Xie; Wei Jia; Linda L. Wong

doi:10.3390/diagnostics9040167

journal article Open Access Oct 29, 2019

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

Erin B. Evangelista Sandi A. Kwee

Miles M. Sato

Lu Wang

Christoph Rettenmeier Guoxiang Xie Wei Jia

Linda L. Wong

Diagnostics Vol. 9 No. 4 pp. 167 · MDPI AG

View at Publisher Save 10.3390/diagnostics9040167

Abstract

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.

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Citations

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References

Details

Published: Oct 29, 2019
Vol/Issue: 9(4)
Pages: 167
License: View

Authors

E

Erin B. Evangelista

The Queen’s Medical Center, Honolulu, HI 96813, USA

S

Sandi A. Kwee

The Queen’s Medical Center, Honolulu, HI 96813, USA; University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI 96813, USA; Departments of Medicine and Surgery, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA

M

Miles M. Sato

The Queen’s Medical Center, Honolulu, HI 96813, USA

L

Lu Wang

University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI 96813, USA

C

Christoph Rettenmeier

Departments of Medicine and Surgery, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA

G

Guoxiang Xie

University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI 96813, USA

W

Wei Jia

University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI 96813, USA

L

Linda L. Wong

University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI 96813, USA; Departments of Medicine and Surgery, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA

Funding

National Institutes of Health Award: R01CA161209-06

Cite This Article

Erin B. Evangelista, Sandi A. Kwee, Miles M. Sato, et al. (2019). Phospholipids are A Potentially Important Source of Tissue Biomarkers for Hepatocellular Carcinoma: Results of a Pilot Study Involving Targeted Metabolomics. Diagnostics, 9(4), 167. https://doi.org/10.3390/diagnostics9040167

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

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