| 英文摘要 |
Metabolomics is considered an effective approach for understanding metabolic responsesin complex biological systems. Accordingly, it has attracted increasing attention forbiomarker discovery, especially in cancer. In this study, we used a non-invasive method toevaluate four urine metabolite biomarker candidatesdo-phosphoethanolamine, 3-amio-2-piperidone, uridine and 5-hydroxyindoleactic aciddfor their potential as bladder cancerdiagnostic biomarkers. To analyze these targeted amine- and phenol-containing metabolites,we used differential 12C2-/13C2-dansylation labeling coupled with liquid chromatography/tandem mass spectrometry, which has previously been demonstrated to exhibithigh sensitivity and reproducibility. Specifically, we used ultra-performance liquid chromatography(UPLC) coupled with high-resolution Fourier transform ion-cyclotron resonanceMS system (LC-FT/MS) and an ion trap MS with MRM function (LC-HCT/MS) fortargeted quantification. The urinary metabolites of interest were well separated andquantified using this approach. To apply this approach to clinical urine specimens, wespiked samples with 13C2-dansylatedsynthetic compounds, which served as standards fortargeted quantification of 12C2-dansylated urinary endogenous metabolites using LC-FT/MS as well as LC-HCT/MS with MRM mode. These analyses revealed significant differences intwo of the four metabolites of interestdo-phosphoethanolamine and uridinedbetweenbladder cancer and non-cancer groups. O-phosphoethanolamine was the most promisingsingle biomarker, with an area-under-the-curve (AUC) value of 0.709 for bladder cancerdiagnosis. Diagnostic performance was improved by combining uridine and o-phosphoethanolaminein a marker panel, yielding an AUC value of 0.726. This study confirmeddiscovery-phase features of the urine metabolome of bladder cancer patients and verifiedtheir importance for further study. |
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