Large-scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival

Venkatrao Vantaku, Sri Ramya Donepudi, Danthasinghe Waduge Badrajee Piyarathna, Chandra Sekhar Amara, Chandrashekar R. Ambati, Wei Tang, Vasanta Putluri, Darshan S. Chandrashekar, Sooryanarayana Varambally, Martha Kennedy Terris, Kimberly Davies, Stefan Ambs, Roni Jacob Bollag, Andrea B. Apolo, Arun Sreekumar, Nagireddy Putluri

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)921-932
Number of pages12
JournalCancer
Volume125
Issue number6
DOIs
StatePublished - Mar 15 2019

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Metabolic Networks and Pathways
Urinary Bladder Neoplasms
African Americans
Survival
Serum
Metabolomics
Metabolome
Atlases
Taurine
Glutamine
Lipid Metabolism
Aspartic Acid
Serine
Lysine
Glutamic Acid
Spectrum Analysis
Nucleotides
Amino Acids

Keywords

  • bladder cancer
  • liquid chromatography–mass spectrometry (LC-MS)
  • metabolomics
  • racial disparity
  • serum

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Large-scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival. / Vantaku, Venkatrao; Donepudi, Sri Ramya; Piyarathna, Danthasinghe Waduge Badrajee; Amara, Chandra Sekhar; Ambati, Chandrashekar R.; Tang, Wei; Putluri, Vasanta; Chandrashekar, Darshan S.; Varambally, Sooryanarayana; Terris, Martha Kennedy; Davies, Kimberly; Ambs, Stefan; Bollag, Roni Jacob; Apolo, Andrea B.; Sreekumar, Arun; Putluri, Nagireddy.

In: Cancer, Vol. 125, No. 6, 15.03.2019, p. 921-932.

Research output: Contribution to journalArticle

Vantaku, V, Donepudi, SR, Piyarathna, DWB, Amara, CS, Ambati, CR, Tang, W, Putluri, V, Chandrashekar, DS, Varambally, S, Terris, MK, Davies, K, Ambs, S, Bollag, RJ, Apolo, AB, Sreekumar, A & Putluri, N 2019, 'Large-scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival', Cancer, vol. 125, no. 6, pp. 921-932. https://doi.org/10.1002/cncr.31890
Vantaku, Venkatrao ; Donepudi, Sri Ramya ; Piyarathna, Danthasinghe Waduge Badrajee ; Amara, Chandra Sekhar ; Ambati, Chandrashekar R. ; Tang, Wei ; Putluri, Vasanta ; Chandrashekar, Darshan S. ; Varambally, Sooryanarayana ; Terris, Martha Kennedy ; Davies, Kimberly ; Ambs, Stefan ; Bollag, Roni Jacob ; Apolo, Andrea B. ; Sreekumar, Arun ; Putluri, Nagireddy. / Large-scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival. In: Cancer. 2019 ; Vol. 125, No. 6. pp. 921-932.
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title = "Large-scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival",
abstract = "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.",
keywords = "bladder cancer, liquid chromatography–mass spectrometry (LC-MS), metabolomics, racial disparity, serum",
author = "Venkatrao Vantaku and Donepudi, {Sri Ramya} and Piyarathna, {Danthasinghe Waduge Badrajee} and Amara, {Chandra Sekhar} and Ambati, {Chandrashekar R.} and Wei Tang and Vasanta Putluri and Chandrashekar, {Darshan S.} and Sooryanarayana Varambally and Terris, {Martha Kennedy} and Kimberly Davies and Stefan Ambs and Bollag, {Roni Jacob} and Apolo, {Andrea B.} and Arun Sreekumar and Nagireddy Putluri",
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T1 - Large-scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival

AU - Vantaku, Venkatrao

AU - Donepudi, Sri Ramya

AU - Piyarathna, Danthasinghe Waduge Badrajee

AU - Amara, Chandra Sekhar

AU - Ambati, Chandrashekar R.

AU - Tang, Wei

AU - Putluri, Vasanta

AU - Chandrashekar, Darshan S.

AU - Varambally, Sooryanarayana

AU - Terris, Martha Kennedy

AU - Davies, Kimberly

AU - Ambs, Stefan

AU - Bollag, Roni Jacob

AU - Apolo, Andrea B.

AU - Sreekumar, Arun

AU - Putluri, Nagireddy

PY - 2019/3/15

Y1 - 2019/3/15

N2 - 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.

AB - 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.

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KW - metabolomics

KW - racial disparity

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