Lysophosphatidic Acid is a Biomarker for Peritoneal Carcinomatosis of Gastric Cancer and Correlates with Poor Prognosis

Zeng, Ruolan; Li, Bin; Huang, Jianyi; Zhong, Meizuo; Li, Li; Duan, Chaojun; Zeng, Shan; Huang, Jin; Liu, Wei; Lu, Jinmiao; Tang, Youhong; Zhou, Lingming; Liu, Yiping; Li, Jianhuang; He, Zhengxi; Wang, Quan; Dai, Yaozhang

doi:10.1089/gtmb.2017.0060

Cited by 26 publications

(19 citation statements)

References 65 publications

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“…Elevated ATX levels have been observed in the blood and malignant tissues from patients with thyroid [ 102 ], lung [ 103 ], breast [ 104 ], liver [ 105 ], pancreatic [ 106 , 107 ], kidney [ 108 ], bladder [ 108 ], and prostate cancer [ 109 ]. As a consequence, LPA levels increase in those cancers [ 107 , 110 , 111 , 112 , 113 ], which has been considered an indicator of poor prognosis [ 110 , 113 ]. Significantly, LPA concentrations have been reported to reach as high as 10 μM in the ascites fluid of ovarian cancer patients [ 73 , 74 , 75 ].…”

Section: Upregulation Of Lpa Signaling In Cancersmentioning

confidence: 99%

Lipid Phosphate Phosphatases and Cancer

Tang

Brindley

2020

Biomolecules

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Lipid phosphate phosphatases (LPPs) are a group of three enzymes (LPP1–3) that belong to a phospholipid phosphatase (PLPP) family. The LPPs dephosphorylate a wide spectrum of bioactive lipid phosphates, among which lysophosphatidate (LPA) and sphingosine 1-phosphate (S1P) are two important extracellular signaling molecules. The LPPs are integral membrane proteins, which are localized on plasma membranes and intracellular membranes, including the endoplasmic reticulum and Golgi network. LPPs regulate signaling transduction in cancer cells and demonstrate different effects in cancer progression through the breakdown of extracellular LPA and S1P and other intracellular substrates. This review is intended to summarize an up-to-date understanding about the functions of LPPs in cancers.

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Section: Upregulation Of Lpa Signaling In Cancersmentioning

confidence: 99%

Lipid Phosphate Phosphatases and Cancer

Tang

Brindley

2020

Biomolecules

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“…Therefore, new ways to manage the disease are needed and this is likely to come from the identification of new therapeutic targets. ATX, which is encoded by the ENPP2 gene, is responsible for the generation of LPA from LPC and has been shown to be overexpressed in a number of tumour types, such as melanoma ( Sun et al, 2016 ) and cancers of the thyroid ( Benesch et al, 2015 ), breast ( Yang et al, 2002 ), pancreas ( Nakai et al, 2011 ) and stomach ( Zeng et al, 2017 ), leading to increased levels of LPA in tumours ( Nakai et al, 2011 ; Zeng et al, 2017 ). In the present study, we show that LPA metabolism is de-regulated in OSCCs.…”

Section: Discussionmentioning

confidence: 99%

Deregulation of lysophosphatidic acid metabolism in oral cancer promotes cell migration via the up-regulation of COX-2

Rahman

Tan

Johnson

et al. 2020

PeerJ

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Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide and accounts for 300,000 new cases yearly. The five-year survival rate is approximately 50% and the major challenges to improving patient prognosis include late presentation, treatment resistance, second primary tumours and the lack of targeted therapies. Therefore, there is a compelling need to develop novel therapeutic strategies. In this study, we have examined the effect of lysophosphatidic acid (LPA) on OSCC cell migration, invasion and response to radiation, and investigated the contribution of cyclooxygenase-2 (COX-2) in mediating the tumour promoting effects of LPA. Using the TCGA data set, we show that the expression of the lipid phosphate phosphatases (LPP), LPP1 and LPP3, was significantly down-regulated in OSCC tissues. There was no significant difference in the expression of the ENPP2 gene, which encodes for the enzyme autotaxin (ATX) that produces LPA, between OSCCs and control tissues but ENPP2 levels were elevated in a subgroup of OSCCs. To explore the phenotypic effects of LPA, we treated OSCC cell lines with LPA and showed that the lipid enhanced migration and invasion as well as suppressed the response of the cells to irradiation. We also show that LPA increased COX-2 mRNA and protein levels in OSCC cell lines and inhibition of COX-2 activity with the COX-2 inhibitor, NS398, attenuated LPA-induced OSCC cell migration. Collectively, our data show for the first time that COX-2 mediates some of the pro-tumorigenic effects of LPA in OSCC and identifies the ATX-LPP-LPA-COX-2 pathway as a potential therapeutic target for this disease.

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“…Furthermore, metabolic parameters were examined as indicators of PD. For instance, levels of lysophosphatidic acid were elevated in GC malignant ascites and significantly reduced after intraperitoneal chemotherapy [125]. Dopa decarboxylase levels showed sensitivity of 87% and specificity of 98% for diagnosis of synchronous PD [122].…”

Section: Molecular Markers In Peritoneal Lavagesmentioning

confidence: 99%

Predicting Peritoneal Dissemination of Gastric Cancer in the Era of Precision Medicine: Molecular Characterization and Biomarkers

Chen

Zhou

Wang

et al. 2020

Cancers

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Gastric cancer (GC) is a leading cause of worldwide cancer-related death. Being a highly heterogeneous disease, the current treatment of GC has been suboptimal due to the lack of subtype-dependent therapies. Peritoneal dissemination (PD) is a common pattern of GC metastasis associated with poor prognosis. Therefore, it is urgently necessary to identify patients at high risk of PD. PD is found to be associated with Lauren diffuse type GC. Molecular profiling of GC, especially diffuse type GC, has been utilized to identify molecular alterations and has given rise to various molecular classifications, shedding light on the underlying mechanism of PD and enabling identification of patients at higher PD risk. In addition, a series of diagnositc and prognostic biomarkers of PD from serum, peritoneal lavages and primary GCs have been reported. This comprehensive review summarizes findings on the multi-omic characteristics of diffuse type GC, the clinical significance of updating molecular classifications of GC in association with PD risk and research advances in PD-associated biomarkers.

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Lysophosphatidic Acid is a Biomarker for Peritoneal Carcinomatosis of Gastric Cancer and Correlates with Poor Prognosis

Abstract: This study demonstrated that LPA levels in plasma and ascites may be useful diagnostic biomarkers for PC of gastric cancer and that higher levels are associated with poor prognosis.

Cited by 26 publications

References 65 publications

Lipid Phosphate Phosphatases and Cancer

Lipid Phosphate Phosphatases and Cancer

Deregulation of lysophosphatidic acid metabolism in oral cancer promotes cell migration via the up-regulation of COX-2

Predicting Peritoneal Dissemination of Gastric Cancer in the Era of Precision Medicine: Molecular Characterization and Biomarkers

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