title: Feasibility of detecting prostate cancer by ultraperformance liquid chromatography-mass spectrometry serum metabolomics.
abstract: Prostate cancer (PCa) is the second leading cause of cancer-related mortality in men. The prevalent diagnosis method is based on the serum prostate-specific antigen (PSA) screening test, which suffers from low specificity, overdiagnosis, and overtreatment. In this work, untargeted metabolomic profiling of age-matched serum samples from prostate cancer patients and healthy individuals was performed using ultraperformance liquid chromatography coupled to high-resolution tandem mass spectrometry (UPLC-MS/MS) and machine learning methods. A metabolite-based in vitro diagnostic multivariate index assay (IVDMIA) was developed to predict the presence of PCa in serum samples with high classification sensitivity, specificity, and accuracy. A panel of 40 metabolic spectral features was found to be differential with 92.1% sensitivity, 94.3% specificity, and 93.0% accuracy. The performance of the IVDMIA was higher than the prevalent PSA test. Within the discriminant panel, 31 metabolites were identified by MS and MS/MS, with 10 further confirmed chromatographically by standards. Numerous discriminant metabolites were mapped in the steroid hormone biosynthesis pathway. The identification of fatty acids, amino acids, lysophospholipids, and bile acids provided further insights into the metabolic alterations associated with the disease. With additional work, the results presented here show great potential toward implementation in clinical settings.
authors.affiliation: School of Chemistry and Biochemistry, ‡College of Computing, §School of Biology, Integrated Cancer Research Center, and ∥Parker H. Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zang
authors.forename: Christina M
authors.initials: CM
authors.lastname: Jones
authors.forename: Tran Q
authors.initials: TQ
authors.lastname: Long
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Monge
authors.forename: Manshui
authors.initials: M
authors.lastname: Zhou
authors.forename: L DeEtte
authors.initials: LD
authors.lastname: Walker
authors.forename: Roman
authors.initials: R
authors.lastname: Mezencev
authors.forename: Alexander
authors.initials: A
authors.lastname: Gray
authors.forename: John F
authors.initials: JF
authors.lastname: McDonald
authors.forename: Facundo M
authors.initials: FM
authors.lastname: Fernández
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000302:isolation & purification; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D005240:Feasibility Studies; D006801:Humans; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor