High level of phosphatidylcholines/lysophosphatidylcholine ratio in urine is associated with prostate cancer

Li, Xin; Nakayama, Kenji; Goto, Takayuki; Kimura, Hiroko; Akamatsu, Shusuke; Hayashi, Yujiro; Fujita, Kazutoshi; Kobayashi, Takashi; Shimizu, Kōji; Nonomura, Norio; Ogawa, Osamu; Inoue, Takahiro

doi:10.1111/cas.15093

Cited by 18 publications

(11 citation statements)

References 48 publications

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“…One interesting urinary metabolite that was increased after an 8 Gy exposure was LPC (22:6) at the sn-2 position, which we differentiated from the sn-1 isomer based on retention time and the characteristic lack of a choline fragment ion ( m/z 104.1) (; https://doi.org/10.1667/RADE-22-00211.1.S1). Perturbation of urinary LPC levels have been reported in certain diseases, such as prostate cancer ( 39 ) and fast progression diabetic kidney disease ( 40 ), but typically urinary lipid levels are difficult to detect unless extracellular vesicles have been isolated ( 42 ). Also, many sn-2 LPC isomers are unstable and isomerize to the sn-1 position, however, this is dependent on acyl saturation where sn-2 LPC (22:6) isomerization is much slower ( 43 ) and LPC acyltransferase (LPCAT3) has been shown to prefer the sn-2 position for binding polyunsaturated fatty acids ( 44 ).…”

Section: Resultsmentioning

confidence: 99%

Variable Dose Rates in Realistic Radiation Exposures: Effects on Small Molecule Markers of Ionizing Radiation in the Murine Model

et al. 2023

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Novel biodosimetry assays for use in preparedness and response to potential malicious attacks or nuclear accidents would ideally provide accurate dose reconstruction independent of the idiosyncrasies of a complex exposure to ionizing radiation. Complex exposures will consist of dose rates spanning the low dose rates (LDR) to very high-dose rates (VHDR) that need to be tested for assay validation. Here, we investigate how a range of relevant dose rates affect metabolomic dose reconstruction at potentially lethal radiation exposures (8 Gy in mice) from an initial blast or subsequent fallout exposures compared to zero or sublethal exposures (0 or 3 Gy in mice) in the first 2 days, which corresponds to an integral time individuals will reach medical facilities after a radiological emergency. Biofluids (urine and serum) were collected from both male and female 9–10-week-old C57BL/6 mice at 1 and 2 days postirradiation (total doses of 0, 3 or 8 Gy) after a VHDR of 7 Gy/s. Additionally, samples were collected after a 2-day exposure consisting of a declining dose rate (1 to 0.004 Gy/min) recapitulating the 7:10 rule-of-thumb time dependency of nuclear fallout. Overall similar perturbations were observed in both urine and serum metabolite concentrations irrespective of sex or dose rate, with the exception of xanthurenic acid in urine (female specific) and taurine in serum (VHDR specific). In urine, we developed identical multiplex metabolite panels (N6,N6,N6-trimethyllysine, carnitine, propionylcarnitine, hexosamine-valine-isoleucine, and taurine) that could identify individuals receiving potentially lethal levels of radiation from the zero or sublethal cohorts with excellent sensitivity and specificity, with creatine increasing model performance at day 1. In serum, individuals receiving a 3 or 8 Gy exposure could be identified from their pre-irradiation samples with excellent sensitivity and specificity, however, due to a lower dose response the 3 vs. 8 Gy groups could not be distinguished from each other. Together with previous results, these data indicate that dose-rate-independent small molecule fingerprints have potential in novel biodosimetry assays.

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Section: Resultsmentioning

confidence: 99%

Variable Dose Rates in Realistic Radiation Exposures: Effects on Small Molecule Markers of Ionizing Radiation in the Murine Model

et al. 2023

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“…Moreover, the content of LPC and LPE were increased inversely, and thus the ratio of PC/LPC was decreased after dandelion extract treatment. The higher content of LPC is beneficial for a better prognosis ( Li et al, 2021b ).…”

Section: Discussionmentioning

confidence: 99%

“…Some cancers rely on two desaturation pathways mediated by stearoyl-coenzyme A desaturase (SCD) and FADS2 to generate unsaturated fatty acids ( Vriens et al, 2019 ). FADS2 is regulated by SREBP and generates unusual fatty acid sapienate, which could replace palmitoleate or oleate produced by SCD in cell membrane synthesis ( Li et al, 2021b ). Hence, only dual inhibition of SCD and FADS2 could result in tumor cell death directly.…”

Section: Discussionmentioning

confidence: 99%

Dandelion extract inhibits triple-negative breast cancer cell proliferation by interfering with glycerophospholipids and unsaturated fatty acids metabolism

et al. 2022

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Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with limited treatment options and a poor prognosis. TNBC exists widely reprogrammed lipid metabolism, and its metabolic-associated proteins and oncometabolites are promising as potential therapeutic targets. Dandelion (Taraxacum mongolicum) is a classical herbal medicine used to treat breast diseases based on traditional Chinese medicine theory and was reported to have antitumor effects and lipid regulatory capacities. Our previous study showed that dandelion extract was effective against TNBC. However, whether dandelion extract could regulate the lipid metabolisms of TNBC and exert its antitumor effects via interfering with lipids metabolism remained unclear. In this study, an integrated approach combined with network pharmacology and multi-omics techniques (including proteomics, metabolomics, and lipidomics) was performed to investigate the potential regulatory mechanisms of dandelion extract against TNBC. We first determined the antitumor effects of dandelion extract in vitro and in vivo. Then, network pharmacology analysis speculated the antitumor effects involving various metabolic processes, and the multi-omics results of the cells, tumor tissues, and plasma revealed the changes in the metabolites and metabolic-associated proteins after dandelion extract treatment. The alteration of glycerophospholipids and unsaturated fatty acids were the most remarkable types of metabolites. Therefore, the metabolism of glycerophospholipids and unsaturated fatty acids, and their corresponding proteins CHKA and FADS2, were considered the primary regulatory pathways and biomarkers of dandelion extract against TNBC. Subsequently, experimental validation showed that dandelion extract decreased CHKA expression, leading to the inhibition of the PI3K/AKT pathway and its downstream targets, SREBP and FADS2. Finally, the molecular docking simulation suggested that picrasinoside F and luteolin in dandelion extract had the most highly binding scores with CHKA, indicating they may be the potential CHKA inhibitors to regulate glycerophospholipids metabolisms of TNBC. In conclusion, we confirmed the antitumor effects of dandelion extract against TNBC cells in vitro and demonstrated that dandelion extract could interfere with glycerophospholipids and unsaturated fatty acids metabolism via downregulating the CHKA expression and inhibiting PI3K/AKT/SREBP/FADS2 axis.

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“…Very recently, two different MALDI-TOF-based studies investigated the suitability of urinary lipids as potential biomarkers for prostate cancer. In the first work, samples from prostate cancer and benign prostatic hyperplasia were considered [ 41 ]. Urine samples collected after digital rectal examination were extracted using the acidified Bligh–Dyer method, and the levels of urinary lysophosphatidylcholine and phosphatidylcholines were compared, finding significant differences between PrC and benign prostatic hyperplasia patients.…”

Section: Urine Samples Analysismentioning

confidence: 99%

MALDI-TOF/MS Analysis of Non-Invasive Human Urine and Saliva Samples for the Identification of New Cancer Biomarkers

Zambonin

Aresta

2022

Molecules

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Cancer represents a group of heterogeneous diseases that are a leading global cause of death. Even though mortality has decreased in the past thirty years for different reasons, most patients are still diagnosed at the advanced stage, with limited therapeutic choices and poor outcomes. Moreover, the majority of cancers are detected using invasive painful methods, such as endoscopic biopsy, making the development of non-invasive or minimally invasive methods for the discovery and fast detection of specific biomarkers a crucial need. Among body fluids, a valuable non-invasive alternative to tissue biopsy, the most accessible and least invasive are undoubtedly urine and saliva. They are easily retrievable complex fluids containing a large variety of endogenous compounds that may provide information on the physiological condition of the body. The combined analysis of these fluids with matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF/MS), a reliable and easy-to-use instrumentation that provides information with relatively simple sample pretreatments, could represent the ideal option to rapidly achieve fast early stage diagnosis of tumors and their real-time monitoring. On this basis, the present review summarizes the recently reported applications relevant to the MALDI analysis of human urine and saliva samples.

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High level of phosphatidylcholines/lysophosphatidylcholine ratio in urine is associated with prostate cancer

Cited by 18 publications

References 48 publications

Variable Dose Rates in Realistic Radiation Exposures: Effects on Small Molecule Markers of Ionizing Radiation in the Murine Model

Variable Dose Rates in Realistic Radiation Exposures: Effects on Small Molecule Markers of Ionizing Radiation in the Murine Model

Dandelion extract inhibits triple-negative breast cancer cell proliferation by interfering with glycerophospholipids and unsaturated fatty acids metabolism

MALDI-TOF/MS Analysis of Non-Invasive Human Urine and Saliva Samples for the Identification of New Cancer Biomarkers

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