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. Cancer 2019;125:921-932.

High-coverage plasma lipidomics reveals novel sex-specific lipidomic fingerprints of age and BMI: Evidence from two large population cohort studies

“…For 506 of these, we provide alkyl, alkenyl, and acyl-chain resolution (e.g., PE(P-18:0/20:4)), whereas only 83 species are reported as the sum totals (e.g., PC(38:2)), with the remainder showing some level of fatty acid definition (e.g., TG (48:2) [neutral loss (NL)-14:0]). Comparable platforms that are able to perform larger cohort studies include the Biocrates AbsoluteIDQ p180 kit, which has been used extensively to provide data on multiple large cohort studies [88,89] but covers a smaller number of lipid classes, with limited structural resolution owing to technical limitations [90,91]. However, we do observe general alignment with our findings; Trabado and colleagues measured 185 plasma metabolites in 924 healthy individuals using the AbsoluteIDQ p180 kit and showed higher lysophosphatidylcholine and lower sphingomyelin and phosphatidylcholine species in men relative to women [91].…”

Δ9-Tetrahydrocannabinol Prevents Mortality from Acute Respiratory Distress Syndrome through the Induction of Apoptosis in Immune Cells, Leading to Cytokine Storm Suppression

“…Metabolites were extracted from serum using the extraction procedure described previously [ 72 , 73 , 74 , 75 , 76 , 77 ]. Briefly, 50 µL of the serum sample was used for the metabolic extraction.…”

Dysregulated Gut Homeostasis Observed Prior to the Accumulation of the Brain Amyloid-β in Tg2576 Mice

“…Changes in circulating vitamin B12 were examined by mass spectrometry. Vitamin B12 was extracted from plasma using liquid-liquid extraction as described in earlier publications [91][92][93]. The HPLC column used was Zorbax eclipse XDB C-18, 1.8 micron, 4.6 × 100 mm Agilent technologies Santa Clara, CA, USA).…”