Urine metallomics signature as an indicator of pancreatic cancer

Kathrin Schilling; Fiona Larner; Amina Saad; Rhiannon Roberts; Hemant M. Kocher; Oleg Blyuss; Alex N. Halliday; Tatjana Crnogorac-Jurcevic

doi:10.1039/D0MT00061B

Urine metallomics signature as an indicator of pancreatic cancer†

Kathrin Schilling,*^ab Fiona Larner,

^ac Amina Saad,^d Rhiannon Roberts,^d Hemant M. Kocher,^d Oleg Blyuss,^ef Alex N. Halliday^b and Tatjana Crnogorac-Jurcevic^g

Author affiliations

* Corresponding authors

^a Department of Earth Sciences, University of Oxford, South Parks Road, UK

^b Lamont-Doherty Earth Observatory, Columbia University, Palisades, NY, USA
E-mail: kathrins@ldeo.coumbia.edu

^c St Catherine's College, Manor Road, Oxford, UK

^d Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, London, UK

^e Wolfson's Institute for Cancer Prevention, Queen Mary University of London, London, UK

^f Department of Paediatrics and Paediatric Infectious Diseases, Sechenov First Moscow State Medical University, Moscow, Russia

^g Centre for Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest types of cancer. Its high mortality rate is attributed largely to the difficulty of early diagnosis. Analysis of urine is an excellent non-invasive approach to trace changes in biochemical reactions due to cancer development. Here we show remarkable differences in concentration of several essential metals: significantly lower levels of urinary calcium and magnesium and increased levels of copper and zinc in PDAC when compared to healthy controls, and demonstrate that a combined analysis of these essential metals are accurate indicators (sensitivity = 99.5%) for metal dyshomeostasis in PDAC. In addition, natural stable zinc isotope composition (δ^66/64Zn) in urine reveals the preferential excretion of isotopically light zinc in PDAC (δ^66/64Zn_median = −0.15‰) compared to healthy controls (δ^66/64Zn_median = +0.02‰), likely supporting the dysregulation of metalloproteins. These findings demonstrate for the first time that metallomics is a promising approach for discovery of biomarkers for detection of patients with PDAC, completely non-invasively, using urine samples.

Metallomics

Urine metallomics signature as an indicator of pancreatic cancer†

Abstract

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