Large-scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival.
Black or African American
/ statistics & numerical data
Amino Acids
/ blood
Case-Control Studies
Chromatography, Liquid
Female
Humans
Lipids
/ blood
Male
Mass Spectrometry
Metabolic Networks and Pathways
Metabolomics
/ methods
Survival Analysis
Urinary Bladder Neoplasms
/ blood
White People
/ statistics & numerical data
bladder cancer
liquid chromatography-mass spectrometry (LC-MS)
metabolomics
racial disparity
serum
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
15 03 2019
15 03 2019
Historique:
received:
14
08
2018
revised:
15
10
2018
accepted:
16
10
2018
pubmed:
3
1
2019
medline:
18
12
2019
entrez:
3
1
2019
Statut:
ppublish
Résumé
African Americans (AAs) experience a disproportionally high rate of bladder cancer (BLCA) deaths even though their incidence rates are lower than those of other patient groups. Using a metabolomics approach, this study investigated how AA BLCA may differ molecularly from European Americans (EAs) BLCA, and it examined serum samples from patients with BLCA with the aim of identifying druggable metabolic pathways in AA patients. Targeted metabolomics was applied to measure more than 300 metabolites in serum samples from 2 independent cohorts of EA and AA patients with BLCA and healthy EA and AA controls via liquid chromatography-mass spectrometry, and this was followed by the identification of altered metabolic pathways with a focus on AA BLCA. A subset of the differential metabolites was validated via absolute quantification with the Biocrates AbsoluteIDQ p180 kit. The clinical significance of the findings was further examined in The Cancer Genomic Atlas BLCA data set. Fifty-three metabolites, mainly related to amino acid, lipid, and nucleotide metabolism, were identified that showed significant differences in abundance between AA and EA BLCA. For example, the levels of taurine, glutamine, glutamate, aspartate, and serine were elevated in serum samples from AA patients versus EA patients. By mapping these metabolites to genes, this study identified significant relations with regulators of metabolism such as malic enzyme 3, prolyl 3-hydroxylase 2, and lysine demethylase 2A that predicted patient survival exclusively in AA patients with BLCA. This metabolic profile of serum samples might be used to assess risk progression in AA BLCA. These first-in-field findings describe metabolic alterations in AA BLCA and emphasize a potential biological basis for BLCA health disparities.
Sections du résumé
BACKGROUND
African Americans (AAs) experience a disproportionally high rate of bladder cancer (BLCA) deaths even though their incidence rates are lower than those of other patient groups. Using a metabolomics approach, this study investigated how AA BLCA may differ molecularly from European Americans (EAs) BLCA, and it examined serum samples from patients with BLCA with the aim of identifying druggable metabolic pathways in AA patients.
METHODS
Targeted metabolomics was applied to measure more than 300 metabolites in serum samples from 2 independent cohorts of EA and AA patients with BLCA and healthy EA and AA controls via liquid chromatography-mass spectrometry, and this was followed by the identification of altered metabolic pathways with a focus on AA BLCA. A subset of the differential metabolites was validated via absolute quantification with the Biocrates AbsoluteIDQ p180 kit. The clinical significance of the findings was further examined in The Cancer Genomic Atlas BLCA data set.
RESULTS
Fifty-three metabolites, mainly related to amino acid, lipid, and nucleotide metabolism, were identified that showed significant differences in abundance between AA and EA BLCA. For example, the levels of taurine, glutamine, glutamate, aspartate, and serine were elevated in serum samples from AA patients versus EA patients. By mapping these metabolites to genes, this study identified significant relations with regulators of metabolism such as malic enzyme 3, prolyl 3-hydroxylase 2, and lysine demethylase 2A that predicted patient survival exclusively in AA patients with BLCA.
CONCLUSIONS
This metabolic profile of serum samples might be used to assess risk progression in AA BLCA. These first-in-field findings describe metabolic alterations in AA BLCA and emphasize a potential biological basis for BLCA health disparities.
Identifiants
pubmed: 30602056
doi: 10.1002/cncr.31890
pmc: PMC6402983
mid: NIHMS996977
doi:
Substances chimiques
Amino Acids
0
Lipids
0
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
921-932Subventions
Organisme : NCI NIH HHS
ID : U01 CA167234
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA220297
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA125123
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA216426
Pays : United States
Informations de copyright
© 2019 American Cancer Society.
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