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

Yagi, T.; Shoaib, Muhammad Harris; Kuschner, Cyrus E.; Nishikimi, Mitsuaki; Becker, Lance B.; Lee, Annette T.; Kim, Junhwan

doi:10.3390/cancers11040520

Cited by 21 publications

(23 citation statements)

References 36 publications

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“…Several studies have found a relationship between plasma LPA levels and ovarian carcinoma; for example, a meta-analysis, comparing LPA levels in the serum of 980 ovarian cancer patients, 872 benign controls and 668 healthy controls, showed higher LPA plasma levels in the cancer group with respect to the benign and healthy control samples [146], thus suggesting that the raised detection of plasma LPA might be a potential diagnostic biomarker. Nonetheless, this finding is not supported by a recent lipidomic study that did not find any change in the content of this lipid in serum of ovarian cancer patients [147]. Discrepancies in the results can be explained taking into the account that, due to its susceptibility to sample processing procedure (e.g., plasma storage time at room temperature and anticoagulant used for blood drawing), LPA can artificially increase.…”

Section: Platelet-derived Bioactive Compoundsmentioning

confidence: 64%

The “Janus Face” of Platelets in Cancer

Catani

Savini

Tullio

et al. 2020

IJMS

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Besides their vital role in hemostasis and thrombosis, platelets are also recognized to be involved in cancer, where they play an unexpected central role: They actively influence cancer cell behavior, but, on the other hand, platelet physiology and phenotype are impacted by tumor cells. The existence of this platelet-cancer loop is supported by a large number of experimental and human studies reporting an association between alterations in platelet number and functions and cancer, often in a way dependent on patient, cancer type and treatment. Herein, we shall report on an update on platelet-cancer relationships, with a particular emphasis on how platelets might exert either a protective or a deleterious action in all steps of cancer progression. To this end, we will describe the impact of (i) platelet count, (ii) bioactive molecules secreted upon platelet activation, and (iii) microvesicle-derived miRNAs on cancer behavior. Potential explanations of conflicting results are also reported: Both intrinsic (heterogeneity in platelet-derived bioactive molecules with either inhibitory or stimulatory properties; features of cancer cell types, such as aggressiveness and/or tumour stage) and extrinsic (heterogeneous characteristics of cancer patients, study design and sample preparation) factors, together with other confounding elements, contribute to “the Janus face” of platelets in cancer. Given the difficulty to establish the univocal role of platelets in a tumor, a better understanding of their exact contribution is warranted, in order to identify an efficient therapeutic strategy for cancer management, as well as for better prevention, screening and risk assessment protocols.

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Section: Platelet-derived Bioactive Compoundsmentioning

confidence: 64%

The “Janus Face” of Platelets in Cancer

Catani

Savini

Tullio

et al. 2020

IJMS

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“…We have also found less abundant phospholipids such as phosphatidylglycerol (PG) and phosphatidylserine (PS), but did not include them in this study due to their insufficient peak intensities, which may be inconsistently detected when interfered by more abundant ions. We also detected LPA and LPI, which we found to be unstable, resulting in exclusion from our study [13].…”

Section: Lc-ms Analysis Of Lysophospholipidsmentioning

confidence: 87%

“…While studies using global lipidomics approaches have reported different plasma phospholipids profiles in ovarian cancer patients, these findings were limited by unsatisfactory sensitivity and/or an absence of benign tumor [9][10][11][12]. Furthermore, the sole use of lysophosphatidic acid (LPA), the most intensively studied phospholipid, also has significant limitations due to the artificial increase during sample processing, storage, and analysis [13].…”

Section: Introductionmentioning

confidence: 99%

Relative Ratios Enhance the Diagnostic Power of Phospholipids in Distinguishing Benign and Cancerous Ovarian Masses

Yagi

Kuschner

Shoaib

et al. 2019

Cancers

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Ovarian cancer remains a highly lethal disease due to its late clinical presentation and lack of reliable early biomarkers. Protein-based diagnostic markers have presented limitations in identifying ovarian cancer. We tested the potential of phospholipids as markers of ovarian cancer by utilizing inter-related regulation of phospholipids, a unique property that allows the use of ratios between phospholipid species for quantitation. High-performance liquid chromatography mass spectrometry was used to measure phospholipid, lysophospholipid, and sphingophospholipid content in plasma from patients with benign ovarian masses, patients with ovarian cancer, and controls. We applied both absolute and relative phospholipid ratios for quantitation. Receiver operating characteristic analysis was performed to test the sensitivity and specificity. We found that utilization of ratios between phospholipid species greatly outperformed absolute quantitation in the identification of ovarian cancer. Of the phospholipids analyzed, species in phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and sphingomyelin (SM) were found to have great biomarker potential. LPC(20:4)/LPC(18:0) carried the greatest capacity to differentiate cancer from control, SM(d18:1/24:1)/SM(d18:1/22:0) to differentiate benign from cancer, and PC(18:0/20:4)/PC(18:0/18:1) to differentiate benign from control. These results demonstrate the potential of plasma phospholipids as a novel marker of ovarian cancer by utilizing the unique characteristics of phospholipids to further enhance the diagnostic power.

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“…There have been some contradictory reports, however, as Baker and colleagues reported that there were no significant differences in the concentrations of either individual LPA values or total LPA in the plasma of ovarian cancer patients compared to normal controls (Baker et al, 2002) and, recently, it was reported that LPA levels were lower in the plasma of ovarian cancer patients (Yagi et al, 2019). These discrepancies have been suggested to be due to the fact that LPA levels in plasma can be artificially increased during sample handling and processing (Yagi et al, 2019). Our data would indicate that total plasma LPA levels per se are not biomarkers for HNSCC.…”

Section: Discussionmentioning

confidence: 99%

Profiling lysophosphatidic acid levels in plasma from head and neck cancer patients

Rahman

Haron

Hollows

et al. 2020

PeerJ

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Head and neck squamous cell carcinoma (HNSCC) represents a significant world health problem, with approximately 600,000 new cases being diagnosed annually. The prognosis for patients with HNSCC is poor and, therefore, the identification of biomarkers for screening, diagnosis and prognostication would be clinically beneficial. A limited number of studies have used lipidomics to profile lipid species in the plasma of cancer patients. However, the profile and levels of lysophosphatidic acid (LPA) species have not been examined in HNSCC. In this study, a targeted lipidomics approach using liquid chromatography triple quadrupole mass spectrometry (LCMS/MS) was used to analyse the concentration of LPA (16:0 LPA, 18:0 LPA, 18:1 LPA, 18:2 LPA and 20:4 LPA) in the plasma of patients with oral squamous cell carcinoma (OSCC) and nasopharyngeal carcinoma (NPC), together with healthy controls. The levels of three LPA species (18:1 LPA, 18:2 LPA and 20:4 LPA) were significantly lower in the plasma of OSCC patients, whilst the concentrations of all five LPA species tested were significantly lower in plasma from NPC patients. Furthermore, the order of abundance of LPA species in plasma was different between the control and cancer groups, with 16:0 LPA, 18:0 LPA levels being more abundant in OSCC and NPC patients. Medium to strong correlations were observed using all pairs of LPA species and a clear separation of the normal and tumour groups was observed using PCA analysis. In summary, the results of this study showed that the levels of several LPA species in the plasma of patients with OSCC and NPC were lower than those from healthy individuals. Understanding these variations may provide novel insights into the role of LPA in these cancers.

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

Cited by 21 publications

References 36 publications

The “Janus Face” of Platelets in Cancer

The “Janus Face” of Platelets in Cancer

Relative Ratios Enhance the Diagnostic Power of Phospholipids in Distinguishing Benign and Cancerous Ovarian Masses

Profiling lysophosphatidic acid levels in plasma from head and neck cancer patients

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