Normalization of urinary pteridines by urine specific gravity for early cancer detection

• Urine specific gravity normalization was studied in urinary pteridines.
• Creatinine adjustment performance was compared relative to urine specific gravity.
• Creatinine may not be an appropriate dilution factor for breast cancer biomarkers.
• Specific gravity corrected pteridines better identify aggressive breast cancers.
• Similar trends were reported in high grade bladder cancers.

BackgroundUrinary 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.Methods6-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.ResultsUSG 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.ConclusionUSG, as a bulk property, can provide better performance over creatinine-based normalizations for urinary pteridines in cancer detection applications.