Metabolic Pathway Signatures Associated with Urinary Metabolite Biomarkers Differentiate Bladder Cancer Patients from Healthy Controls

Kim, Dong-Won; Yun, Seok Joong; Yan, Chunri; Jeong, Pildu; Kim, Ye Hwan; Lee, Il Seok; Kang, Ho Won; Park, Sunghyouk; Moon, Sung Joon; Choi, Yung Hyun; Choi, Young Deuk; Kim, Isaac Yi; Kim, Jayoung; Kim, Wun-Jae

doi:10.3349/ymj.2016.57.4.865

Cited by 37 publications

(34 citation statements)

References 31 publications

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“…Although the potential role of the metabolic pathway in the development of BC has been reported in the previous urine and tissue metabonomic studies3334, AFMK, indolelactic acid and indoleacetic acid were firstly identified as the diagnostic serum biomarkers of BC. Excessive tryptophan metabolites seem to play a role in suppressing antitumor immune responses, thus promoting cancer cells survival, through activation of aryl hydrocarbon receptor, which is involved in carcinogenesis3536.…”

Section: Discussionmentioning

confidence: 99%

Three serum metabolite signatures for diagnosing low-grade and high-grade bladder cancer

Tan

Wang

Yuan

et al. 2017

Sci Rep

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To address the shortcomings of cystoscopy and urine cytology for detecting and grading bladder cancer (BC), ultrahigh performance liquid chromatography (UHPLC) coupled with Q-TOF mass spectrometry in conjunction with univariate and multivariate statistical analyses was employed as an alternative method for the diagnosis of BC. A series of differential serum metabolites were further identified for low-grade(LG) and high-grade(HG) BC patients, suggesting metabolic dysfunction in malignant proliferation, immune escape, differentiation, apoptosis and invasion of cancer cells in BC patients. In total, three serum metabolites including inosine, acetyl-N-formyl-5-methoxykynurenamine and PS(O-18:0/0:0) were selected by binary logistic regression analysis, and receiver operating characteristic (ROC) test based on their combined use for HG BC showed that the area under the curve (AUC) was 0.961 in the discovery set and 0.950 in the validation set when compared to LG BC. Likewise, this composite biomarker panel can also differentiate LG BC from healthy controls with the AUC of 0.993 and 0.991 in the discovery and validation set, respectively. This finding suggested that this composite serum metabolite signature was a promising and less invasive classifier for probing and grading BC, which deserved to be further investigated in larger samples.

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Section: Discussionmentioning

confidence: 99%

Three serum metabolite signatures for diagnosing low-grade and high-grade bladder cancer

Tan

Wang

Yuan

et al. 2017

Sci Rep

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“…Altered tryptophan metabolism is linked to cancer development and progression [119, 120]. In particular, indoleamine 2,3-dioxygenase 1 (IDO1), an enzyme involved in tryptophan degradation, has been documented to have therapeutic potential, alone or in combination with chemotherapy or immunotherapy [121].…”

Section: Discussionmentioning

confidence: 99%

How interacting pathways are regulated by miRNAs in breast cancer subtypes

Cava

Colaprico²,

Bertoli

et al. 2016

BMC Bioinformatics

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BackgroundAn important challenge in cancer biology is to understand the complex aspects of the disease. It is increasingly evident that genes are not isolated from each other and the comprehension of how different genes are related to each other could explain biological mechanisms causing diseases. Biological pathways are important tools to reveal gene interaction and reduce the large number of genes to be studied by partitioning it into smaller paths. Furthermore, recent scientific evidence has proven that a combination of pathways, instead than a single element of the pathway or a single pathway, could be responsible for pathological changes in a cell.ResultsIn this paper we develop a new method that can reveal miRNAs able to regulate, in a coordinated way, networks of gene pathways. We applied the method to subtypes of breast cancer. The basic idea is the identification of pathways significantly enriched with differentially expressed genes among the different breast cancer subtypes and normal tissue. Looking at the pairs of pathways that were found to be functionally related, we created a network of dependent pathways and we focused on identifying miRNAs that could act as miRNA drivers in a coordinated regulation process.ConclusionsOur approach enables miRNAs identification that could have an important role in the development of breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-1196-1) contains supplementary material, which is available to authorized users.

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“…Recent metabolomics studies have proven valuable in identifying urinary biomarkers for BCa diagnosis, 36,37 but obtaining an accurate and sensitive noninvasive diagnosis biomarker of human BCa remains a challenging problem. In our study, a pattern based on four urinary metabolites was found to have high accuracy for BCa distinction, and a pattern based on three urinary metabolites, indolylacryloylglycine, N 2 -galacturonyl-L-lysine, and aspartyl-glutamate, was found to have high accuracy for BCa grading distinction.…”

Section: Bca Biomarker Discoverymentioning

confidence: 99%

Investigation of the urinary metabolic variations and the application in bladder cancer biomarker discovery

Liu

Cheng

Liu

et al. 2018

Intl Journal of Cancer

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Urine metabolomics have been used to identify biomarkers for clinical diseases. However, inter-individual variations and effect factors need to be further evaluated. In our study, we explored the urine metabolome in a cohort of 203 health adults, 6 patients with benign bladder lesions, and 53 patients with bladder cancer (BCa) using liquid chromatography coupled with high resolution mass spectrometry. Inter-individual analysis of both healthy controls and BCa patients showed that the urine metabolome was relatively stable. Further analysis indicated that sex and age affect inter-individual variations in urine metabolome. Metabolic pathways such as tryptophan metabolism, the citrate cycle, and pantothenate and CoA biosynthesis were found to be related to sex and age. To eliminate age and sex interference, additional BCa urine metabolomic biomarkers were explored using age and sex-matched urine samples (Test group: 44 health adults vs. 33 patients with BCa). Metabolic profiling of urine could significantly differentiate the cases with cancer from the controls and high-grade from low-grade BCa. A metabolite panel consisting of trans-2-dodecenoylcarnitine, serinyl-valine, feruloyl-2-hydroxyputrescine, and 3-hydroxynonanoyl carnitine were discovered to have good predictive ability for BCa with an area under the curve (AUC) of 0.956 (cross validation: AUC = 0.924). A panel of indolylacryloylglycine, N -galacturonyl-L-lysine, and aspartyl-glutamate was used to establish a robust model for high- and low-grade BCa distinction with AUC of 0.937 (cross validation: AUC = 0.891). External sample (26 control vs. 20 BCa) validation verified the acceptable accuracy of these models for BCa detection. Our study showed that urinary metabolomics is a useful strategy for differential analysis and biomarker discovery.

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Metabolic Pathway Signatures Associated with Urinary Metabolite Biomarkers Differentiate Bladder Cancer Patients from Healthy Controls

Cited by 37 publications

References 31 publications

Three serum metabolite signatures for diagnosing low-grade and high-grade bladder cancer

Three serum metabolite signatures for diagnosing low-grade and high-grade bladder cancer

How interacting pathways are regulated by miRNAs in breast cancer subtypes

Investigation of the urinary metabolic variations and the application in bladder cancer biomarker discovery

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