Copper Ceruloplasmin as a Potential Biomarker of Biliary Tract Cancers: A Pilot Study
6 affiliations
- 1Department of Environmental Sciences, Jožef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia
- 2Jožef Stefan International Postgraduate School, Jamova 39, 1000 Ljubljana, Slovenia
- 3Department of Medical Oncology, Institute of Oncology Ljubljana, Zaloška cesta 2, 1000 Ljubljana, Slovenia
- 4Medical Faculty, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia
- 5Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloška cesta 2, 1000 Ljubljana, Slovenia
- 6Faculty of Health Sciences, University of Primorska, Polje 42, 6310 Izola, Slovenia
Abstract
Copper (Cu) and its distribution among circulating Cu-binding proteins may be altered in cancer and could provide diagnostic or prognostic information. However, the specificity of individual Cu species as biomarkers of biliary tract cancers (BTCs) remains unclear. In this pilot study, we investigated Cu speciation in serum samples from 10 patients with BTCs before and after chemotherapy or immuno-chemotherapy and 10 healthy individuals. Cu species were separated using conjoint liquid chromatography (CLC) with inductively coupled plasma mass spectrometry (ICP-MS) detection. The CLC column, comprising two immunoaffinity (α-HSA) and one DEAE anion-exchange disk, separated Cu bound to ceruloplasmin (Cu-Cp), low-molecular-mass (Cu-LMM), and human serum albumin (Cu-HSA) species, which were quantified by isotope dilution ICP-MS or protein standard–based quantification. Cu speciation analysis revealed that Cu-Cp concentrations followed total serum Cu concentrations in patients with BTCs before and after chemotherapy or immuno-chemotherapy and in healthy individuals, while Cu-HSA and Cu-LMM concentrations also decreased. Cu-Cp accounted for approximately 90% of total serum Cu across all groups, and there were no significant differences in its relative contribution to total Cu. Cu-Cp accounted for approximately 90% of total serum Cu across the investigated groups, with no statistically significant differences in its relative contribution. These preliminary findings suggest that changes in Cu-Cp concentrations largely reflect changes in total serum Cu rather than BTC-specific alterations in Cu distribution. Therefore, Cu-Cp is unlikely to serve as a specific biomarker for BTCs. However, further studies involving larger patient cohorts are needed to establish the potential diagnostic and prognostic relevance of Cu-Cp in BTCs.
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BibTeX
@article{kozlica2026copper,
title = {{Copper Ceruloplasmin as a Potential Biomarker of Biliary Tract Cancers: A Pilot Study}},
author = {Katarina Kozlica and Radmila Milačič Ščančar and Stefan Marković and Martina Reberšek and Maja Čemažar and Saša Kupčič and Ajda Medved and Janez Ščančar},
journal = {Biomolecules},
year = {2026},
month = nov,
doi = {10.3390/biom16111604},
url = {https://www.mdpi.com/2218-273X/16/11/1604},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Copper Ceruloplasmin as a Potential Biomarker of Biliary Tract Cancers: A Pilot Study
AU - Katarina Kozlica
AU - Radmila Milačič Ščančar
AU - Stefan Marković
AU - Martina Reberšek
AU - Maja Čemažar
AU - Saša Kupčič
AU - Ajda Medved
AU - Janez Ščančar
PY - 2026
DA - 2026/11/03
JO - Biomolecules
DO - 10.3390/biom16111604
UR - https://www.mdpi.com/2218-273X/16/11/1604
AB - Copper (Cu) and its distribution among circulating Cu-binding proteins may be altered in cancer and could provide diagnostic or prognostic information. However, the specificity of individual Cu species as biomarkers of biliary tract cancers (BTCs) remains unclear. In this pilot study, we investigated Cu speciation in serum samples from 10 patients with BTCs before and after chemotherapy or immuno-chemotherapy and 10 healthy individuals. Cu species were separated using conjoint liquid chromatography (CLC) with inductively coupled plasma mass spectrometry (ICP-MS) detection. The CLC column, comprising two immunoaffinity (α-HSA) and one DEAE anion-exchange disk, separated Cu bound to ceruloplasmin (Cu-Cp), low-molecular-mass (Cu-LMM), and human serum albumin (Cu-HSA) species, which were quantified by isotope dilution ICP-MS or protein standard–based quantification. Cu speciation analysis revealed that Cu-Cp concentrations followed total serum Cu concentrations in patients with BTCs before and after chemotherapy or immuno-chemotherapy and in healthy individuals, while Cu-HSA and Cu-LMM concentrations also decreased. Cu-Cp accounted for approximately 90% of total serum Cu across all groups, and there were no significant differences in its relative contribution to total Cu. Cu-Cp accounted for approximately 90% of total serum Cu across the investigated groups, with no statistically significant differences in its relative contribution. These preliminary findings suggest that changes in Cu-Cp concentrations largely reflect changes in total serum Cu rather than BTC-specific alterations in Cu distribution. Therefore, Cu-Cp is unlikely to serve as a specific biomarker for BTCs. However, further studies involving larger patient cohorts are needed to establish the potential diagnostic and prognostic relevance of Cu-Cp in BTCs.
SN - 2218-273X
ER -