Press release: Possible test for liver cancer…

18 August 2015

Possible test for liver cancer using technology for analysing rocks and minerals

May be first biochemical test for liver cancer

A group of clinicians and geochemists are working to develop a test for the most common form of primary liver cancer, HCC (Hepatocellular Carcinoma). HCC kills over 600,000 people worldwide every year. It usually develops from chronic liver disease such as hepatitis or cirrhosis, but there is no good biochemical test to indicate when the cancer develops, meaning that even for patients most at risk, it is nearly impossible to know when a cancer may develop until symptoms appear. Now a multi-national group of scientists are developing a new test for HCC, based on methods used to measure the stable isotope compositions of rocks and minerals.

Elements in nature tend to have different isotopes (the same number of protons, but different numbers of neutrons). So for example, in nature, 99% of the carbon is stable carbon-12, 1% is stable carbon-13, and radioactive carbon-14 occurs in trace amounts. This distribution of stable isotopes also occurs with other elements, such as copper and sulphur.

It has been known for some time that in cancer, the body’s copper regulation can be affected. The researchers decided to look at whether the ratios of different copper isotopes varied between HCC patients and normal controls. They compared 23 male HCC patients with 20 controls; they found that the blood of patients with liver cancer had an enriched quantity of certain isotopes in comparison to control patients.

Comparing copper isotopes 65Cu and 63Cu, they found that HCC patients have around 0.4 parts per thousand more 63Cu relative to 65Cu than the control patients. This difference was also seen with the Sulphur isotopes 32S and 34S, with blood of patients with HCC is around 1.5 parts per thousand richer in 32S relative to 34S than is normally found.

Group leader, geochemist Vincent Balter (Lyon, France) said

“The findings are interesting and potentially significant. We found that the ratio of 65Cu to 63Cu was higher in the blood of cancer patients than in the blood of controls. Preliminary results seem to show that these ratios are in fact reversed in the tumours themselves, which implies that there is a partition of isotopes between the blood and the tumour.

This opens the way for a blood test. At the moment the results are preliminary, but if we can confirm the validity of an isotopic test for HCC, this might have a significant impact on patients who have chronic liver disease, who risk developing liver cancer”.

He continued:

“There is increasing evidence that copper metabolism is significant in many cancers, and recently it has been found that copper chelation agents, which mop up copper in the body, can slow and perhaps even halt the growth of some tumours. What we have found may go some way to explaining some of the mechanisms of the growth of these tumours”

Speaking for the Goldschmidt conference, Associate Professor Rob Newton of the University of Leeds said:

“This is an example of how techniques developed for one field can transfer to another. The type of isotopic analysis used by Balter and colleagues is commonly used in Earth Sciences, from studies on the Moon’s formation to those on past changes in ocean and atmosphere chemistry.

I am excited by the idea that one could make isotopic mass balances between organs as we are used to doing between Earth reservoirs like the mantle and crust. They will have, however, to face new difficulties, for instance a significant variability in the isotopic measurements, a common feature of biological samples, and to develop cheap, high throughput and user friendly methods for sample preparation and analysis. However, it’s likely that we will continue to see exciting new applications of these isotopic techniques in other fields as this study shows.”


Notes for Editors
Please mention the Goldschmidt conference in any story resulting from this press release
Contact details
Dr Vincent Balter
Robert Newton
Goldschmidt Press Officer, Tom Parkhill: tel +39 349 238 8191
The Goldschmidt Conference is the world’s most important geochemistry conference. Around 3000 delegates will attend the 25th Anniversary 2015 Goldschmidt conference in Prague ( , from 16-21 August. The Goldschmidt Conference is co-sponsored by the Geochemical Society and the European Association of Geochemistry. Goldschmidt2016 takes place in Yokohama, Japan.

Copper and sulfur isotope variations in liver cancer VINCENT BALTER1*, ANDRE NOGUEIRA DA COSTA2, VICTOR PAKY BONDANESE1, KLERVIA JAOUEN3, ALINE LAMBOUX1, SULEEPORN SANGRAJRANG4, NICOLAS VINCENT1, FRANÇOIS FOUREL1, PHILIPPE TÉLOUK1, MICHELLE GIGOU5, CHRISTOPHE LÉCUYER1,6, PETCHARIN SRIVATANAKUL4, CHRISTIAN BRÉCHOT5,7, FRANCIS ALBARÈDE1, PIERRE HAINAUT8 1 UMR 5276, Laboratoire de Géologie de Lyon. École Normale Supérieure de Lyon, CNRS, Université de Lyon1. France (*correspondence:Vincent.Balter@enslyon. fr) 2 Mechanistic Toxicology & Molecular Pathology Department of Non-Clinical Development UCB BioPharma, SPRL Chemin du Foriest, 1 B-1420 Braine L’Alleud, Belgium 3 Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz, 6, 04103 Leipzig, Germany 4. National Cancer Institute, Bangkok, Rama VI road, Ratchathewi, Bangkok 10400, Thailand 5 Unité 785, Pathogénèse et Traitement de l’Hépatite Fulminante et du Cancer du Foie. Inserm, Université Paris-Sud, Villejuif, France 6 Institut Universitaire de France 7 Institut Pasteur. 25-28 rue du Docteur Roux. 75015 Paris, France 8 Institut Albert Bonniot, UJF INSERM 823 Grenoble and Strathclyde Institute of Global Public health, International Prevention Research Institute, 69006 Lyon, France.
In cancer, copper concentrations increase in the blood and in tumor cells, leading to deleterious side effects. The mechanisms of this copper accumulation and the source of extra copper burden are still poorly understood. We show that in hepatocellular carcinoma (HCC) patients, blood copper is enriched in 63Cu compared to control subjects and demonstrate that this isotopic signature is not compatible with a dietary origin. It rather reflects the massive reallocation in the body of copper immobilized within cysteine-rich proteins such as metallothioneins. We also show that the blood of HCC patients is enriched in 32S compared to control subjects, an enrichment compatible with the notion that at least 6% of blood sulfur originates from tumor-derived sulphides. We will discuss how the hypoxic conditions of the tumor microenvironment can impair the metabolism of copper and sulfur, notably by changing their redox state and, as a consequence, their ability to bind specific molecules.

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