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Int. J. Mol. Sci. 2017, 18(2), 410; doi:10.3390/ijms18020410

Expression of Iron-Related Proteins Differentiate Non-Cancerous and Cancerous Breast Tumors

1
Unit of Medical Statistics, Biometry and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
2
Proteomics Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
3
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy
4
DOSMM, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
5
Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China
6
Molecular Targets Unit, Fondazione IRCCS Istituto Nazionale dei Tumouri, 20133 Milan, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Sanjay K. Srivastava
Received: 19 December 2016 / Revised: 1 February 2017 / Accepted: 6 February 2017 / Published: 14 February 2017
(This article belongs to the Special Issue Precision Medicine—From Bench to Bedside)
View Full-Text   |   Download PDF [951 KB, uploaded 16 February 2017]   |  

Abstract

We have previously reported hepcidin and ferritin increases in the plasma of breast cancer patients, but not in patients with benign breast disease. We hypothesized that these differences in systemic iron homeostasis may reflect alterations in different iron-related proteins also play a key biochemical and regulatory role in breast cancer. Thus, here we explored the expression of a bundle of molecules involved in both iron homeostasis and tumorigenesis in tissue samples. Enzyme-linked immunosorbent assay (ELISA) or reverse-phase protein array (RPPA), were used to measure the expression of 20 proteins linked to iron processes in 24 non-cancerous, and 56 cancerous, breast tumors. We found that cancerous tissues had higher level of hepcidin than benign lesions (p = 0.012). The univariate analysis of RPPA data highlighted the following seven proteins differentially expressed between non-cancerous and cancerous breast tissue: signal transducer and transcriptional activator 5 (STAT5), signal transducer and activator of transcription 3 (STAT3), bone morphogenetic protein 6 (BMP6), cluster of differentiation 74 (CD74), transferrin receptor (TFRC), inhibin alpha (INHA), and STAT5_pY694. These findings were confirmed for STAT5, STAT3, BMP6, CD74 and INHA when adjusting for age. The multivariate statistical analysis indicated an iron-related 10-protein panel effective in separating non-cancerous from cancerous lesions including STAT5, STAT5_pY694, myeloid differentiation factor 88 (MYD88), CD74, iron exporter ferroportin (FPN), high mobility group box 1 (HMGB1), STAT3_pS727, TFRC, ferritin heavy chain (FTH), and ferritin light chain (FTL). Our results showed an association between some iron-related proteins and the type of tumor tissue, which may provide insight in strategies for using iron chelators to treat breast cancer. View Full-Text
Keywords: Iron; metabolism; breast cancer; hepcidin; ferroportin; transferrin receptor (TFR); STAT5; reverse phase protein array; iron chelators Iron; metabolism; breast cancer; hepcidin; ferroportin; transferrin receptor (TFR); STAT5; reverse phase protein array; iron chelators
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Pizzamiglio, S.; De Bortoli, M.; Taverna, E.; Signore, M.; Veneroni, S.; Cho, W.C.-S.; Orlandi, R.; Verderio, P.; Bongarzone, I. Expression of Iron-Related Proteins Differentiate Non-Cancerous and Cancerous Breast Tumors. Int. J. Mol. Sci. 2017, 18, 410.

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