title: Urinary metallomics as a novel biomarker discovery platform: Breast cancer as a case study.
abstract: BACKGROUND
  Urinary metallomics is presented here as a new "omics" approach that aims to facilitate personalized cancer screening and prevention by improving our understanding of urinary metals in disease.
  
  
  METHODS
  Twenty-two urinary metals were examined with inductively-coupled plasma-mass spectrometry in 138 women newly diagnosed with breast cancer and benign conditions. Urinary metals from spot urine samples were adjusted to renal dilution using urine specific gravity.
  
  
  RESULTS
  Two urinary metals, copper (P-value=0.036) and lead (P-value=0.003), were significantly increased in the urine of breast cancer patients. A multivariate model that comprised copper, lead, and patient age afforded encouraging discriminatory power (AUC: 0.728, P-value<0.0005), while univariate models of copper (61.7% sensitivity, 50.0% specificity) and lead (76.6% sensitivity, 51.2% specificity) at optimized cutoff thresholds compared favorably with other breast cancer diagnostic modalities such as mammography. Correlations found among various metals suggested potential geographic and dietary influences on the urine metallome that warrant further investigation.
  
  
  CONCLUSIONS
  This proof-of-concept work introduces urinary metallomics as a noninvasive, potentially transformative "omics" approach to early cancer detection. Urinary copper and lead have also been preliminarily identified as potential breast cancer biomarkers.
authors.affiliation: Department of Chemistry, Center for Single Nanoparticle, Single Cell, and Single Molecule Monitoring, Missouri University of Science and Technology, Rolla, MO 65409, United States.
authors.forename: Casey
authors.initials: C
authors.lastname: Burton
authors.affiliation: Department of Chemistry, Center for Single Nanoparticle, Single Cell, and Single Molecule Monitoring, Missouri University of Science and Technology, Rolla, MO 65409, United States.
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Dan
authors.affiliation: Department of Chemistry, Center for Single Nanoparticle, Single Cell, and Single Molecule Monitoring, Missouri University of Science and Technology, Rolla, MO 65409, United States.
authors.forename: Ariel
authors.initials: A
authors.lastname: Donovan
authors.affiliation: Department of Chemistry, Center for Single Nanoparticle, Single Cell, and Single Molecule Monitoring, Missouri University of Science and Technology, Rolla, MO 65409, United States.
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Center for Single Nanoparticle, Single Cell, and Single Molecule Monitoring, Missouri University of Science and Technology, Rolla, MO 65409, United States.
authors.forename: Honglan
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Chemistry, Center for Single Nanoparticle, Single Cell, and Single Molecule Monitoring, Missouri University of Science and Technology, Rolla, MO 65409, United States. Electronic address: yinfa@mst.edu.
authors.forename: Yinfa
authors.initials: Y
authors.lastname: Ma
authors.affiliation: PerkinElmer, Inc., 940 Winter Street, Waltham, MA 02451, United States.
authors.forename: Cynthia P
authors.initials: CP
authors.lastname: Bosnak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000652:urine*; D003300:Copper / Q000652:urine*; D005260:Female; D006801:Humans; D007854:Lead / Q000652:urine*; D013058:Mass Spectrometry; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor; D007854:Lead; D003300:Copper
keywords: Breast cancer metallomics; ICP-MS; Noninvasive breast cancer screening; Urinary copper; Urinary lead; Urinary metallomics