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

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 accoun...

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Autores principales: Yagi, Tsukasa, Shoaib, Muhammad, Kuschner, Cyrus E., Nishikimi, Mitsuaki, Becker, Lance B., Lee, Annette T., Kim, Junhwan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521627/
https://www.ncbi.nlm.nih.gov/pubmed/30979045
http://dx.doi.org/10.3390/cancers11040520
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author Yagi, Tsukasa
Shoaib, Muhammad
Kuschner, Cyrus E.
Nishikimi, Mitsuaki
Becker, Lance B.
Lee, Annette T.
Kim, Junhwan
author_facet Yagi, Tsukasa
Shoaib, Muhammad
Kuschner, Cyrus E.
Nishikimi, Mitsuaki
Becker, Lance B.
Lee, Annette T.
Kim, Junhwan
author_sort Yagi, Tsukasa
collection PubMed
description 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.
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spelling pubmed-65216272019-05-31 Challenges and Inconsistencies in Using Lysophosphatidic Acid as a Biomarker for Ovarian Cancer Yagi, Tsukasa Shoaib, Muhammad Kuschner, Cyrus E. Nishikimi, Mitsuaki Becker, Lance B. Lee, Annette T. Kim, Junhwan Cancers (Basel) Article 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. MDPI 2019-04-11 /pmc/articles/PMC6521627/ /pubmed/30979045 http://dx.doi.org/10.3390/cancers11040520 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yagi, Tsukasa
Shoaib, Muhammad
Kuschner, Cyrus E.
Nishikimi, Mitsuaki
Becker, Lance B.
Lee, Annette T.
Kim, Junhwan
Challenges and Inconsistencies in Using Lysophosphatidic Acid as a Biomarker for Ovarian Cancer
title Challenges and Inconsistencies in Using Lysophosphatidic Acid as a Biomarker for Ovarian Cancer
title_full Challenges and Inconsistencies in Using Lysophosphatidic Acid as a Biomarker for Ovarian Cancer
title_fullStr Challenges and Inconsistencies in Using Lysophosphatidic Acid as a Biomarker for Ovarian Cancer
title_full_unstemmed Challenges and Inconsistencies in Using Lysophosphatidic Acid as a Biomarker for Ovarian Cancer
title_short Challenges and Inconsistencies in Using Lysophosphatidic Acid as a Biomarker for Ovarian Cancer
title_sort challenges and inconsistencies in using lysophosphatidic acid as a biomarker for ovarian cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521627/
https://www.ncbi.nlm.nih.gov/pubmed/30979045
http://dx.doi.org/10.3390/cancers11040520
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