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

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.

Cancer. 2019 Jan 02 [Epub ahead of print]

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 K Terris, Kimberly Davies, Stefan Ambs, Roni Bollag, Andrea B Apolo, Arun Sreekumar, Nagireddy Putluri

Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, Texas., Dan L. Duncan Cancer Center, Advanced Technology Core, Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, Texas., Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Department of Pathology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama., Augusta University, Augusta, Georgia., Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.