Diagnostic Value of Total Plasma Lysophosphatidic Acid in Ovarian Cancer

Lu, Zhaolian; Chen, Yingjian; Hu, Zhide; Hu, Chengjin

doi:10.1097/igc.0000000000000319

Cited by 13 publications

(13 citation statements)

References 35 publications

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“…Previous studies have shown that LPA levels are elevated in the ascites of ovarian cancer patients, most probably due to increased LPA production by cancer cells and the surrounding mesothelium (36,37,(41)(42)(43). The potential contribution of GPAM to this process is not known, thus justifying further investigation into its role in this disease.…”

Section: Discussionmentioning

confidence: 97%

Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma

et al. 2017

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Glycerophosphodiesterase EDI3 (GPCPD1; GDE5; GDPD6) has been suggested to promote cell migration, adhesion, and spreading, but its mechanisms of action remain uncertain. In this study, we targeted the glycerol-3-phosphate acyltransferase GPAM along with choline kinase-a (CHKA), the enzymes that catabolize the products of EDI3 to determine which downstream pathway is relevant for migration. Our results clearly showed that GPAM influenced cell migration via the signaling lipid lysophosphatidic acid (LPA), linking it with GPAM to cell migration. Analysis of GPAM expression in different cancer types revealed a significant association between high GPAM expression and reduced overall survival in ovarian cancer. Silencing GPAM in ovarian cancer cells decreased cell migration and reduced the growth of tumor xenografts. In contrast to these observations, manipulating CHKA did not influence cell migration in the same set of cell lines. Overall, our findings show how GPAM influences intracellular LPA levels to promote cell migration and tumor growth.

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Section: Discussionmentioning

confidence: 97%

Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma

et al. 2017

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“…There are several studies indicating that plasma LPA is promising diagnostic marker for ovarian cancer (for meta-analysis see [21]). LPA concentrations in ovarian cancer patients are elevated already in the early stages of the disease [17].…”

Section: Introductionmentioning

confidence: 99%

Lysophosphatidic acid plasma concentrations in healthy subjects: circadian rhythm and associations with demographic, anthropometric and biochemical parameters

et al. 2017

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BackgroundLysophosphatidic acid (LPA) is a bioactive lipid with a wide biological activity. Previous studies have shown its potential usefulness as a diagnostic marker for ovarian cancer. The aim of the study was to investigate which factors may influence plasma LPA concentrations in healthy subjects and to propose reference values.MethodsThe study group consisted of 100 healthy subjects. From all of them the blood samples were taken at 7 a.m. (fasting state). From 40 volunteers additional blood samples were taken at 2 p.m., at 8 p.m. and at 2 a.m. next morning. Concentrations of LPA were measured in plasma samples using enzyme-linked immunosorbent assay.ResultsAnalysis of samples from 100 healthy volunteers showed significant influence of sex and age on plasma LPA. The reference range for the plasma LPA concentration corrected for age and sex, determined at 2.5–97.5 percentile interval is 0.14–1.64 μM. LPA correlates positively with BMI, serum total cholesterol, triacylglycerols, uric acid and negatively with estimated glomerular filtration rate and serum albumin. Concentration of LPA at 2 a.m. was lower than at 2 p.m. There were not any significant differences between plasma LPA at 7 a.m. and any other time of the day.ConclusionsPlasma LPA is associated with demographic, anthropometric and biochemical parameters. It seems that LPA concentrations have no specific circadian rhythm and the time of donation and fasting state have marginal effect on plasma LPA. These findings may be helpful in future incorporation of LPA as a diagnostic marker.

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“…We initially reported LPA as a potential marker for ovarian cancer (OC) [72], which is supported by blinded [22] and numerous independent studies [73,74,75,76,77,78,79,80,81]. LPA was also shown to be a biomarker for other gynecological cancers [72], as well as for gastric cancer [82].…”

Section: Lpa: From Bench To Bedsidementioning

confidence: 95%

Targeting Lysophosphatidic Acid in Cancer: The Issues in Moving from Bench to Bedside

2019

Cancers

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Since the clear demonstration of lysophosphatidic acid (LPA)’s pathological roles in cancer in the mid-1990s, more than 1000 papers relating LPA to various types of cancer were published. Through these studies, LPA was established as a target for cancer. Although LPA-related inhibitors entered clinical trials for fibrosis, the concept of targeting LPA is yet to be moved to clinical cancer treatment. The major challenges that we are facing in moving LPA application from bench to bedside include the intrinsic and complicated metabolic, functional, and signaling properties of LPA, as well as technical issues, which are discussed in this review. Potential strategies and perspectives to improve the translational progress are suggested. Despite these challenges, we are optimistic that LPA blockage, particularly in combination with other agents, is on the horizon to be incorporated into clinical applications.

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Diagnostic Value of Total Plasma Lysophosphatidic Acid in Ovarian Cancer

Cited by 13 publications

References 35 publications

Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma

Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma

Lysophosphatidic acid plasma concentrations in healthy subjects: circadian rhythm and associations with demographic, anthropometric and biochemical parameters

Targeting Lysophosphatidic Acid in Cancer: The Issues in Moving from Bench to Bedside

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