Dataset Information

Metabolite marker discovery for the detection of bladder cancer by comparative metabolomics.

ABSTRACT: Bladder cancer is one of the most common urinary tract carcinomas in the world. Urine metabolomics is a promising approach for bladder cancer detection and marker discovery since urine is in direct contact with bladder epithelia cells; metabolites released from bladder cancer cells may be enriched in urine samples. In this study, we applied ultra-performance liquid chromatography time-of-flight mass spectrometry to profile metabolite profiles of 87 samples from bladder cancer patients and 65 samples from hernia patients. An OPLS-DA classification revealed that bladder cancer samples can be discriminated from hernia samples based on the profiles. A marker discovery pipeline selected six putative markers from the metabolomic profiles. An LLE clustering demonstrated the discriminative power of the chosen marker candidates. Two of the six markers were identified as imidazoleacetic acid whose relation to bladder cancer has certain degree of supporting evidence. A machine learning model, decision trees, was built based on the metabolomic profiles and the six marker candidates. The decision tree obtained an accuracy of 76.60%, a sensitivity of 71.88%, and a specificity of 86.67% from an independent test.

SUBMITTER: Shao CH

PROVIDER: S-EPMC5503573 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Metabolite marker discovery for the detection of bladder cancer by comparative metabolomics.

Shao Chi-Hung CH Chen Chien-Lun CL Lin Jia-You JY Chen Chao-Jung CJ Fu Shu-Hsuan SH Chen Yi-Ting YT Chang Yu-Sun YS Yu Jau-Song JS Tsui Ke-Hung KH Juo Chiun-Gung CG Wu Kun-Pin KP

Oncotarget 20170601 24

Bladder cancer is one of the most common urinary tract carcinomas in the world. Urine metabolomics is a promising approach for bladder cancer detection and marker discovery since urine is in direct contact with bladder epithelia cells; metabolites released from bladder cancer cells may be enriched in urine samples. In this study, we applied ultra-performance liquid chromatography time-of-flight mass spectrometry to profile metabolite profiles of 87 samples from bladder cancer patients and 65 sam ...[more]

PMID: 28415579

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Project description:Background: Clinical outcomes of bladder cancer (BC) are tightly associated with the stage and grade of the initial diagnosis of BC because early detection is clearly important for patients with BC. However, the diagnostic capability of current detection methods, such as urinary cytology, cystoscopy, imageology method, and several urine-based tests, is inadequate for early detection of BC. The objective of our study is to discover novel biomarkers for detecting BC at an early stage, called non-muscle invasive (NMI) BC, using liquid chromatography-high resolution mass spectrometry (LC-HRMS)-based metabolomics. Methods: First, morning midstream urine samples were collected from healthy adult and NMIBC patients. The LC-HRMS-based metabolomics were applied to distinguish the NMIBC group without hematuria from the controls (gender- and age-matched volunteers with normal clinically healthy index), low-grade NMIBC from the controls, and high-grade from low-grade NMIBC. Results: A total of 284 subjects were enrolled in our study including 117 healthy adults, 80 NMIBC patients without hematuria, and 87 NMIBC patients with hematuria. The metabolite panel including dopamine 4-sulfate, MG00/1846Z,9Z,12Z,15Z/00, aspartyl-histidine, and tyrosyl-methionine was found in a discovery set, which showed the predictive ability to distinguish the NMIBC group from the control group with an area under the curve (AUC) of 0.838 in an external validation set. The AUC of the panel for low-grade NMIBC samples, which consisted of 3-hydroxy-cis-5-tetradecenoylcarnitine, 6-ketoestriol, beta-cortolone, tetrahydrocorticosterone, and heptylmalonic acid, was 0.899. The sensitivity and specificity were 0.881 and 0.786, respectively. The AUC of the panel for distinction of low-grade NMIBC with and without hematuria against high-grade NMIBC with and without hematuria were 0.827 and 0.755, respectively. In addition, metabolites involved in tryptophan metabolism were upregulated in the urine of high-grade NMIBC patients when compared with low-grade NMIBC patients with the presence or absence of hematuria. Conclusion: The NMIBC urine metabolic profiling was able to assist in the early detection of BC. Panels of metabolites were discovered to have a potential value for high-grade NMIBC and low-grade NMIBC diagnosis as well as for NMIBC grading distinction.

Dataset Information

Metabolite marker discovery for the detection of bladder cancer by comparative metabolomics.

Publications

Metabolite marker discovery for the detection of bladder cancer by comparative metabolomics.

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