Rapid Screening of Phospholipid Biomarker Candidates from Prostate Cancer Urine Samples by Multiple Reaction Monitoring of UPLC-ESI-MS/MS and Statistical Approaches

Lim, Sangsoo; Bang, Dae Young; Rha, Koon Ho; Moon, Myeong Hee

doi:10.5012/bkcs.2014.35.4.1133

Cited by 5 publications

(3 citation statements)

References 33 publications

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“…Abnormal lipid metabolism is one of the most prominent metabolic changes in cancer. In recent years, lipidomics has made many advances in the study of clinical diseases, such as liver cancer [ 31 ], breast cancer, prostate cancer [ 32 ], colorectal cancer [ 33 ]. Lipid metabolism also plays an important role in the early development of many cancers.…”

Section: Discussionmentioning

confidence: 99%

Super-enhancer-associated INSM2 regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma

et al. 2022

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Background Abnormal lipid metabolism is one of the most prominent metabolic changes in cancer. Studies have shown that lipid metabolism also plays an important role in neuroblastoma. We recently discovered that the insulinoma-associated 2 gene (INSM2) could regulate lipid metabolism in neuroblastoma (NB) and is improperly controlled by super enhancers, a mammalian genome region that has been shown to control the expression of NB cell identity genes. However, the specific molecular pathways by which INSM2 leads to NB disease development are unknown. Results We identified INSM2 as a gene regulated by super enhancers in NB. In addition, INSM2 expression levels were significantly upregulated in NB and correlated with poor prognosis in patients. We found that INSM2 drives the growth of NB cell lines both in vitro and in vivo. Knocking down INSM2 inhibited fatty acid metabolism in NB cells. Mechanistically, INSM2 regulates the expression of SREBP1 by regulating the mTOR signaling pathway, which in turn affects lipid metabolism, thereby mediating the occurrence and development of neuroblastoma. Conclusion INSM2 as a super-enhancer-associated gene could regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma.

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Section: Discussionmentioning

confidence: 99%

Super-enhancer-associated INSM2 regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma

et al. 2022

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“…To this extent, it is essential to develop reproducible quantitative analytical techniques to capture the diversity of lipid metabolites. Previously, either targeted or Orbitrap empowered high resolution discovery workflows have been utilized for lipidomic analysis of urine [16,17]. However, no workflow has been described that provides unbiased direct infusion MS/MS ALL analysis of human urine.…”

Section: Introductionmentioning

confidence: 99%

Dynamic Assessment of Functional Lipidomic Analysis in Human Urine

Rockwell¹,

Gao²,

Chen³

et al. 2016

Lipids

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The development of enabling mass spectrometry platforms for the quantification of diverse lipid species in human urine is of paramount importance for understanding metabolic homeostasis in normal and pathophysiological conditions. Urine represents a non-invasive biofluid that can capture distinct differences in an individual's physiological status. However, currently there is a lack of quantitative workflows to engage in high throughput lipidomic analysis. This study describes the development of a MS/MS(ALL) shotgun lipidomic workflow and a micro liquid chromatography-high resolution tandem mass spectrometry (LC-MS/MS) workflow for urine structural and mediator lipid analysis, respectively. This workflow was deployed to understand biofluid sample handling and collection, extraction efficiency, and natural human variation over time. Utilization of 0.5 mL of urine for structural lipidomic analysis resulted in reproducible quantification of more than 600 lipid molecular species from over 20 lipid classes. Analysis of 1 mL of urine routinely quantified in excess of 55 mediator lipid metabolites comprised of octadecanoids, eicosanoids, and docosanoids generated by lipoxygenase, cyclooxygenase, and cytochrome P450 activities. In summary, the high-throughput functional lipidomics workflow described in this study demonstrates an impressive robustness and reproducibility that can be utilized for population health and precision medicine applications.

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“…Rapid technical advances in MS have facilitated the determination of lipid molecular structures along with quantitative evaluation of diverse lipids at the molecular level. Combining the techniques of liquid chromatography (LC) with MS via electrospray ionization (ESI) has expanded the range of analytical performance in identifying as many lipids as possible, owing to the decrease in ionization suppression from the highly abundant species. − Recently, lipidomic analysis with LC-MS has been attempted to investigate lipid profiles in patient plasma or urine samples in various diseases, such as colorectal cancer, breast cancer, , diabetes, prostate cancer, , and Gaucher’s disease . Specifically, the use of nanoflow LC using capillary columns, prior to MS, is effective in acquiring an enhanced resolution of separation and also improves the sensitivity of detection at low levels (up to femtomolar levels) of lipid species, , owing to the reduced consumption of LC solvents.…”

Section: Introductionmentioning

confidence: 99%

Lipidomic Perturbations in Lung, Kidney, and Liver Tissues of p53 Knockout Mice Analyzed by Nanoflow UPLC-ESI-MS/MS

et al. 2016

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Lipids are important signaling molecules regulating biological processes under normal and diseased conditions. Although p53 mutation is well-known for causing cancer, the relationship between p53-related tumorigenesis and altered lipid profile is unclear. We profiled differences in lipid expressions in liver, lung, and kidney in p53 knockout (KO) mice by high-speed quantitative analysis of 320 lipids (399 species identified) using nanoflow ultrahigh performance liquid chromatography−tandem mass spectrometry (nUPLC-MS/MS). Lung tissues were most severely affected by the lack of p53 gene, as shown by significant reduction (24−44%, P < 0.05) in total phosphatidylcholine (PC), phosphatidylethanolamine (PE), sphingomyelin (SM), diacylglycerol (DG), and triacylglycerol (TG), and significant increases (30−50%) in phosphatidylserine (PS), phosphatidylinositol (PI), and monohexosylceramide (MHC). MHC levels increased in all tissues. Dihexosylceramide (DHC) level decreased only in kidney tissue. Most PI, PS, and phosphatidic acid (PA) species showing significant increases contained a saturated acyl chain (18:0) in lung and liver tissues. Neutral glycerolipids (16:0/22:0-DG and most TGs with saturated and monounsaturated acyl chains) decreased 2−4-fold in the liver tissue. Our results suggest that the lack of p53 and altered lipid profiles are closely related, but as their changes vary from one tissue to another, the lipid alterations are tissue-specific.

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Rapid Screening of Phospholipid Biomarker Candidates from Prostate Cancer Urine Samples by Multiple Reaction Monitoring of UPLC-ESI-MS/MS and Statistical Approaches

Cited by 5 publications

References 33 publications

Super-enhancer-associated INSM2 regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma

Super-enhancer-associated INSM2 regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma

Dynamic Assessment of Functional Lipidomic Analysis in Human Urine

Lipidomic Perturbations in Lung, Kidney, and Liver Tissues of p53 Knockout Mice Analyzed by Nanoflow UPLC-ESI-MS/MS

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