We thank De Marco et al. for their valuable comments regarding TFF1, one of the biomarkers in our panel for early detection of pancreatic adenocarcinoma (PDAC).
We concur with the authors that TFF1 plays an important role in this malignancy, and find the information on the importance of copper binding to TFF1 of great interest. We have previously reported on deregulation of several proteins that bind copper in PDAC,1,2 and increased levels of this metal element have previously been described in both tissue and serum of patients with pancreatic malignancy.3,4 In fact, tissue copper levels were also found to be negatively associated with patient’s survival.4 This is not particularly surprising, considering the important role of this metal in cancer, as increased intra-tumoural copper and/or altered systemic copper distribution was shown to play an important role in cancer growth, angiogenesis, motility and metastases. In that respect, targeting copper in cancer therapy5 and testing metal complexes based on copper as a novel therapeutic approach (of note, platinum-based chemotherapy has been in use for over 40 years!), as highlighted by the authors, appears to be very promising.
Furthermore, we have recently reported that metal disbalance in PDAC can be detected via deregulated levels of several metals in urine, including increased level of urinary copper, which may potentially serve as a diagnostic and/or prognostic marker in pancreatic cancer.6 Thus, mechanistic studies on the effects of copper and its binding partners, as well as testing the potential of copper as novel therapeutic and a potential biomarker seem highly warranted.
References
Crnogorac-Jurcevic, T., Gangeswaran, R., Bhakta, V., Capurso, G., Lattimore, S., Akada, M. et al. Proteomic analysis of chronic pancreatitis and pancreatic adenocarcinoma. Gastroenterology 129, 1454–1463 (2005).
Crnogorac-Jurcevic, T., Missiaglia, E., Blaveri, E., Gangeswaran, R., Jones, M., Terris, B. et al. Molecular alterations in pancreatic carcinoma: expression profiling shows that dysregulated expression of S100 genes is highly prevalent. J. Pathol. 201, 63–74 (2003).
Lener, M. R., Scott, R. J., Wiechwska-Kozlowska, A., Serrano-Fernandez, P., Baszuk, P., Jaworska-Bieniek, K. et al. Serum concentrations of selenium and copper in patients diagnosed with pancreatic cancer. Cancer Res. Treat. 48, 1056–1064 (2016).
Yu, Z., Zhou, R., Zhao, Y., Pan, Y., Liang, H., Zhang, J. S. et al. Blockage of SLC31A1-dependent copper adsorption increases pancreatic cancer cell autophagy to resist cell death. Cell Prolif. 52, 12568 (2019).
Denoyer, D., Masaldan, S., La Fontaine, S. & Cate, M. A. Targeting copper in cancer therapy: ‘Copper That Cancer’. Metallomics 7, 1459–1476 (2015).
Schilling, K., Larner, F., Saad, A., Roberts, R., Kocher, H. M., Blyuss, O. et al. Urine metallomics signature as an indicator of pancreatic cancer. Metallomics 12, 752–757 (2020).
Author information
Authors and Affiliations
Contributions
Paper writing: O.B. and T.C.J.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
Not applicable.
Consent to publish
Not applicable.
Data availability
Not applicable.
Competing interests
The authors declare no competing interests.
Funding information
Not applicable.
Additional information
Note This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Blyuss, O., Crnogorac-Jurcevic, T. Response to the comment on “Development of PancRISK, a urine biomarker-based risk score for stratified screening of pancreatic cancer patients”. Br J Cancer 123, 1468 (2020). https://doi.org/10.1038/s41416-020-1014-4
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41416-020-1014-4
