title: Normalization of urinary pteridines by urine specific gravity for early cancer detection.
abstract: BACKGROUND
  Urinary biomarkers, such as pteridines, require normalization with respect to an individual's hydration status and time since last urination. Conventional creatinine-based corrections are affected by a multitude of patient factors whereas urine specific gravity (USG) is a bulk specimen property that may better resist those same factors. We examined the performance of traditional creatinine adjustments relative to USG to six urinary pteridines in aggressive and benign breast cancers.
  
  
  METHODS
  6-Biopterin, neopterin, pterin, 6-hydroxymethylpterin, isoxanthopterin, xanthopterin, and creatinine were analyzed in 50 urine specimens with a previously developed liquid chromatography-tandem mass spectrometry technique. Creatinine and USG performance were evaluated with non-parametric Mann-Whitney hypothesis testing.
  
  
  RESULTS
  USG and creatinine were moderately correlated (r=0.857) with deviations occurring in dilute and concentrated specimens. In 48 aggressive and benign breast cancers, normalization by USG significantly outperformed creatinine adjustments which marginally outperformed uncorrected pteridines in predicting pathological status. In addition, isoxanthopterin and xanthopterin were significantly higher in pathological specimens when normalized by USG.
  
  
  CONCLUSIONS
  USG, as a bulk property, can provide better performance over creatinine-based normalizations for urinary pteridines in cancer detection applications.
authors.affiliation: Department of Chemistry and Center for Biomedical Science & Engineering, MO University of Science and Technology, Rolla, MO 65409, United States.
authors.forename: Casey
authors.initials: C
authors.lastname: Burton
authors.affiliation: Department of Chemistry and Center for Biomedical Science & Engineering, MO University of Science and Technology, Rolla, MO 65409, United States.
authors.forename: Honglan
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Chemistry and Center for Biomedical Science & Engineering, MO University of Science and Technology, Rolla, MO 65409, United States. Electronic address: yinfa@mst.edu.
authors.forename: Yinfa
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine; D001943:Breast Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000652:urine; D003937:Diagnosis, Differential; D055088:Early Detection of Cancer / Q000379:methods* / Q000592:standards*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011621:Pteridines / Q000652:urine*; D012015:Reference Standards; D013046:Specific Gravity; D016482:Urinalysis / Q000379:methods* / Q000592:standards*; D014556:Urine / Q000737:chemistry*
chemical_list: D014408:Biomarkers, Tumor; D011621:Pteridines
keywords: Breast cancer; Creatinine; Pteridine; Renal dilution; Urine normalization; Urine specific gravity