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Cancers 2019, 11(4), 520; https://doi.org/10.3390/cancers11040520

Challenges and Inconsistencies in Using Lysophosphatidic Acid as a Biomarker for Ovarian Cancer

1
Center for Immunology and Inflammation, Feinstein Institute for Medical Research, 350 Community Dr., Manhasset, NY 11030, USA
2
Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 500 Hofstra Blvd, Hempstead, NY 11549, USA
3
Robert S. Boas Center for Genomics & Human Genetics, Feinstein Institute for Medical Research, 350 Community Dr., Manhasset, NY 11030, USA
*
Author to whom correspondence should be addressed.
Received: 11 March 2019 / Revised: 27 March 2019 / Accepted: 9 April 2019 / Published: 11 April 2019
(This article belongs to the Special Issue Lysophosphatidic Acid Signalling in Cancer)
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Abstract

Increased detection of plasma lysophosphatidic acid (LPA) has been proposed as a potential diagnostic biomarker in ovarian cancer, but inconsistency exists in these reports. It has been shown that LPA can undergo an artificial increase during sample processing and analysis, which has not been accounted for in ovarian cancer research. The aim of this study is to provide a potential explanation about how the artificial increase in LPA may have interfered with previous LPA analysis in ovarian cancer research. Using an established LC-MS method, we measured LPA and other lysophospholipid levels in plasma obtained from three cohorts of patients: non-cancer controls, patients with benign ovarian tumors, and those with ovarian cancer. We did not find the LPA level to be higher in cancer samples. To understand this inconsistency, we observed that LPA content changed more significantly than other lysophospholipids as a function of plasma storage time while frozen. Additionally, only LPA was found to be adversely impacted by incubation time depending on the Ethylenediaminetetraacetic acid (EDTA) concentration used during blood drawing. We also show that the inhibition of autotaxin effectively prevented artificial LPA generation during incubation at room temperature. Our data suggests that the artificial changes in LPA content may contribute to the discrepancies reported in literature. Any future studies planning to measure plasma LPA should carefully design the study protocol to consider these confounding factors. View Full-Text
Keywords: lysophospholipids; LC-MS; diagnosis; lipidomics lysophospholipids; LC-MS; diagnosis; lipidomics
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Yagi, T.; Shoaib, M.; Kuschner, C.E.; Nishikimi, M.; Becker, L.B.; Lee, A.T.; Kim, J. Challenges and Inconsistencies in Using Lysophosphatidic Acid as a Biomarker for Ovarian Cancer. Cancers 2019, 11, 520.

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