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, Fiona Larner, Amina Saad, Rhiannon Roberts, Hemant M Kocher, Oleg Blyuss, Alex N Halliday, Tatjana Crnogorac-Jurcevic

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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 (δ66/64Zn) in urine reveals the preferential excretion of isotopically light zinc in PDAC (δ66/64Znmedian = -0.15‰) compared to healthy controls (δ66/64Znmedian = +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.

Original language	English
Pages (from-to)	752-757
Number of pages	6
Journal	Metallomics
Volume	12
Issue number	5
Early online date	18 Mar 2020
DOIs	https://doi.org/10.1039/d0mt00061b
Publication status	Published - 27 May 2020

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© 2020 Royal Society of Chemistry. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1039/D0MT00061B.
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title = "Urine metallomics signature as an indicator of pancreatic cancer",

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 (δ66/64Zn) in urine reveals the preferential excretion of isotopically light zinc in PDAC (δ66/64Znmedian = -0.15‰) compared to healthy controls (δ66/64Znmedian = +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.",

author = "Kathrin Schilling and Fiona Larner and Amina Saad and Rhiannon Roberts and Kocher, {Hemant M} and Oleg Blyuss and Halliday, {Alex N} and Tatjana Crnogorac-Jurcevic",

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year = "2020",

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T1 - Urine metallomics signature as an indicator of pancreatic cancer

AU - Schilling, Kathrin

AU - Larner, Fiona

AU - Saad, Amina

AU - Roberts, Rhiannon

AU - Kocher, Hemant M

AU - Blyuss, Oleg

AU - Halliday, Alex N

AU - Crnogorac-Jurcevic, Tatjana

PY - 2020/5/27

Y1 - 2020/5/27

N2 - 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 (δ66/64Zn) in urine reveals the preferential excretion of isotopically light zinc in PDAC (δ66/64Znmedian = -0.15‰) compared to healthy controls (δ66/64Znmedian = +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.

AB - 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 (δ66/64Zn) in urine reveals the preferential excretion of isotopically light zinc in PDAC (δ66/64Znmedian = -0.15‰) compared to healthy controls (δ66/64Znmedian = +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.

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EP - 757

JO - Metallomics

JF - Metallomics

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Urine metallomics signature as an indicator of pancreatic cancer

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