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.

Department(s)

Chemistry

Keywords and Phrases

Biological Marker; Copper; Lead; Adult; Aged; Area Under The Curve; Atomic Emission Spectrometry; Biomics; Breast Cancer; Breast Carcinogenesis; Breast Tumor; Cancer Diagnosis; Cancer Growth; Cancer Prognosis; Case Study; Controlled Study; Correlation Analysis; Dilution; Discriminant Analysis; Female; Human; Human Tissue; Immunohistochemistry; Major Clinical Study; Mammography; Pathophysiology; Priority Journal; Receiver Operating Characteristic; Relative Density; Univariate Analysis; Urinalysis; Urinary Metallomics; Urine Level; Very Elderly

International Standard Serial Number (ISSN)

00098981

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2016 Elsevier, All rights reserved.


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