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Research carried out at Oxford, in collaboration with Columbia University and Barts Cancer Institute at Queen Mary University of London, has revealed that the signature of metal ions present in urine samples is an accurate indicator of pancreatic ductal adenocarcinoma (PDAC), one of the deadliest types of cancer.

Diagram showing how metals in urine are affected by pancreatic cancer

The discovery could signal the possibility of a new and completely non-invasive test for pancreatic cancer, of which pancreatic ductal adenocarcinoma (PDAC) is the commonest form, responsible for 90% of pancreatic cancers. Although it accounts for only 2.5% of new cancer cases, pancreatic cancer leads to 6% of cancer deaths worldwide each year because it has an extremely poor prognosis; the mortality rate is around 85%. No tests for early detection are currently available and as symptoms are usually non-specific, PDAC is normally diagnosed at a late stage when it is already locally advanced or has spread to other parts of the body. Any improvement in tests for early detection would therefore represent a breakthrough.

The study, published in Metallomics, took as its starting point the fact that cancer development leads to changes in biochemical reactions within the body. These imbalances, if measurable, can be powerful tools for cancer detection. The research team discovered that PDAC patients had significantly lower levels of urinary calcium and magnesium and increased levels of copper and zinc, when compared to healthy controls. A combined analysis of these essential metals was shown to be an accurate indicator of biochemical changes related to PDAC. The team also identified that the urine of PDAC patients has higher levels of a particular isotope of zinc (‘light zinc’) compared to healthy controls.

Lead author Kathrin Schilling from the Department of Earth Sciences said: “Our results demonstrate for the first time a remarkable difference in essential metal and zinc isotope composition in urine between PDAC patients and healthy people.”

The findings indicate that urine metallomics – the analysis of the types of metal present in the body – is a promising approach for the discovery of biomarkers for detection of patients with PDAC non-invasively, using urine samples.

“As urine samples can be taken time and time again in a non-invasive way, we can start to talk about an effective method to screen and monitor high-risk groups for pancreatic cancer,” Schilling said. “The next steps are to see whether our observations in the pilot study can be expanded to clinical scale studies.

“I am excited to see that highly sensitive isotopic methods originating in the Department of Earth Sciences provide a new opportunity to probe changes in zinc metabolism caused by pancreatic cancer. Our results show that developing new science crossing interdisciplinary boundaries can address really important needs in medicine.”

Senior author on the study, Prof Tatjana Crnogorac-Jurcevic from Queen Mary University of London, said: “We are very excited about our findings, and hope that we will be able to continue this work and further validate obtained results.”

The next step will be to study the levels of metal elements in a larger number of urine samples as well as in pre-diagnostic urine samples, to see if changes in their levels can be detected before the symptoms of cancer appear. If the results are still promising, the metal biomarkers will then be tested in prospectively collected samples, in a real clinical scenario. Barts Cancer Institute has already embarked on UroPanc, a £1.6m study of protein biomarkers in the urine of PDAC patients, funded by the Pancreatic Cancer Research Fund, and samples from this study will be ideal for further validation of the metal biomarkers.

As well as the Department of Earth Sciences, the other research groups involved were:

-          Professor Alex Halliday’s research group at the Lamont-Doherty Earth Observatory, Columbia University, New York

-          Barts Cancer Institute and the Wolfson's Institute for Cancer Prevention, Queen Mary University of London

-          Department of Paediatrics and Paediatric Infectious Diseases, Sechenov First Moscow State Medical University, Moscow