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Targeting amine- and phenol-containing metabolites in urine by dansylation isotope labeling and liquid chromatography mass spectrometry for evaluation of bladder cancer biomarkers
Metabolomics is considered an effective approach for understanding metabolic responses in complex biological systems. Accordingly, it has attracted increasing attention for biomarker discovery, especially in cancer. In this study, we used a non-invasive method to evaluate four urine metabolite bioma...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taiwan Food and Drug Administration
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296201/ https://www.ncbi.nlm.nih.gov/pubmed/30987717 http://dx.doi.org/10.1016/j.jfda.2018.11.008 |
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author | Chen, Yi-Ting Huang, Hsin-Chien Hsieh, Ya-Ju Fu, Shu-Hsuan Li, Liang Chen, Chien-Lun Chu, Lichieh Julie Yu, Jau-Song |
author_facet | Chen, Yi-Ting Huang, Hsin-Chien Hsieh, Ya-Ju Fu, Shu-Hsuan Li, Liang Chen, Chien-Lun Chu, Lichieh Julie Yu, Jau-Song |
author_sort | Chen, Yi-Ting |
collection | PubMed |
description | Metabolomics is considered an effective approach for understanding metabolic responses in complex biological systems. Accordingly, it has attracted increasing attention for biomarker discovery, especially in cancer. In this study, we used a non-invasive method to evaluate four urine metabolite biomarker candidates—o-phosphoethanolamine, 3-amio-2-piperidone, uridine and 5-hydroxyindoleactic acid—for their potential as bladder cancer diagnostic biomarkers. To analyze these targeted amine- and phenol-containing metabolites, we used differential (12)C(2)-/(13)C(2)-dansylation labeling coupled with liquid chromatography/tandem mass spectrometry, which has previously been demonstrated to exhibit high sensitivity and reproducibility. Specifically, we used ultra-performance liquid chromatography (UPLC) coupled with high-resolution Fourier transform ion-cyclotron resonance MS system (LC-FT/MS) and an ion trap MS with MRM function (LC-HCT/MS) for targeted quantification. The urinary metabolites of interest were well separated and quantified using this approach. To apply this approach to clinical urine specimens, we spiked samples with (13)C(2)-dansylatedsynthetic compounds, which served as standards for targeted quantification of (12)C(2)-dansylated urinary endogenous metabolites using LC-FT/MS as well as LC-HCT/MS with MRM mode. These analyses revealed significant differences in two of the four metabolites of interest—o-phosphoethanolamine and uridine—between bladder cancer and non-cancer groups. O-phosphoethanolamine was the most promising single biomarker, with an area-under-the-curve (AUC) value of 0.709 for bladder cancer diagnosis. Diagnostic performance was improved by combining uridine and o-phosphoe-thanolamine in a marker panel, yielding an AUC value of 0.726. This study confirmed discovery-phase features of the urine metabolome of bladder cancer patients and verified their importance for further study. |
format | Online Article Text |
id | pubmed-9296201 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Taiwan Food and Drug Administration |
record_format | MEDLINE/PubMed |
spelling | pubmed-92962012022-08-09 Targeting amine- and phenol-containing metabolites in urine by dansylation isotope labeling and liquid chromatography mass spectrometry for evaluation of bladder cancer biomarkers Chen, Yi-Ting Huang, Hsin-Chien Hsieh, Ya-Ju Fu, Shu-Hsuan Li, Liang Chen, Chien-Lun Chu, Lichieh Julie Yu, Jau-Song J Food Drug Anal Original Article Metabolomics is considered an effective approach for understanding metabolic responses in complex biological systems. Accordingly, it has attracted increasing attention for biomarker discovery, especially in cancer. In this study, we used a non-invasive method to evaluate four urine metabolite biomarker candidates—o-phosphoethanolamine, 3-amio-2-piperidone, uridine and 5-hydroxyindoleactic acid—for their potential as bladder cancer diagnostic biomarkers. To analyze these targeted amine- and phenol-containing metabolites, we used differential (12)C(2)-/(13)C(2)-dansylation labeling coupled with liquid chromatography/tandem mass spectrometry, which has previously been demonstrated to exhibit high sensitivity and reproducibility. Specifically, we used ultra-performance liquid chromatography (UPLC) coupled with high-resolution Fourier transform ion-cyclotron resonance MS system (LC-FT/MS) and an ion trap MS with MRM function (LC-HCT/MS) for targeted quantification. The urinary metabolites of interest were well separated and quantified using this approach. To apply this approach to clinical urine specimens, we spiked samples with (13)C(2)-dansylatedsynthetic compounds, which served as standards for targeted quantification of (12)C(2)-dansylated urinary endogenous metabolites using LC-FT/MS as well as LC-HCT/MS with MRM mode. These analyses revealed significant differences in two of the four metabolites of interest—o-phosphoethanolamine and uridine—between bladder cancer and non-cancer groups. O-phosphoethanolamine was the most promising single biomarker, with an area-under-the-curve (AUC) value of 0.709 for bladder cancer diagnosis. Diagnostic performance was improved by combining uridine and o-phosphoe-thanolamine in a marker panel, yielding an AUC value of 0.726. This study confirmed discovery-phase features of the urine metabolome of bladder cancer patients and verified their importance for further study. Taiwan Food and Drug Administration 2019-01-07 /pmc/articles/PMC9296201/ /pubmed/30987717 http://dx.doi.org/10.1016/j.jfda.2018.11.008 Text en © 2019 Taiwan Food and Drug Administration https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ). |
spellingShingle | Original Article Chen, Yi-Ting Huang, Hsin-Chien Hsieh, Ya-Ju Fu, Shu-Hsuan Li, Liang Chen, Chien-Lun Chu, Lichieh Julie Yu, Jau-Song Targeting amine- and phenol-containing metabolites in urine by dansylation isotope labeling and liquid chromatography mass spectrometry for evaluation of bladder cancer biomarkers |
title | Targeting amine- and phenol-containing metabolites in urine by dansylation isotope labeling and liquid chromatography mass spectrometry for evaluation of bladder cancer biomarkers |
title_full | Targeting amine- and phenol-containing metabolites in urine by dansylation isotope labeling and liquid chromatography mass spectrometry for evaluation of bladder cancer biomarkers |
title_fullStr | Targeting amine- and phenol-containing metabolites in urine by dansylation isotope labeling and liquid chromatography mass spectrometry for evaluation of bladder cancer biomarkers |
title_full_unstemmed | Targeting amine- and phenol-containing metabolites in urine by dansylation isotope labeling and liquid chromatography mass spectrometry for evaluation of bladder cancer biomarkers |
title_short | Targeting amine- and phenol-containing metabolites in urine by dansylation isotope labeling and liquid chromatography mass spectrometry for evaluation of bladder cancer biomarkers |
title_sort | targeting amine- and phenol-containing metabolites in urine by dansylation isotope labeling and liquid chromatography mass spectrometry for evaluation of bladder cancer biomarkers |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296201/ https://www.ncbi.nlm.nih.gov/pubmed/30987717 http://dx.doi.org/10.1016/j.jfda.2018.11.008 |
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