PMID- 28216608 OWN - NLM STAT- MEDLINE DCOM- 20170428 LR - 20181113 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 18 IP - 2 DP - 2017 Feb 14 TI - Expression of Iron-Related Proteins Differentiate Non-Cancerous and Cancerous Breast Tumors. LID - 10.3390/ijms18020410 [doi] LID - 410 AB - 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. FAU - Pizzamiglio, Sara AU - Pizzamiglio S AD - Unit of Medical Statistics, Biometry and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy. sara.pizzamiglio@istitutotumori.mi.it. FAU - De Bortoli, Maida AU - De Bortoli M AD - Proteomics Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy. FAU - Taverna, Elena AU - Taverna E AD - Proteomics Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy. elena.taverna@istitutotumori.mi.it. FAU - Signore, Michele AU - Signore M AD - Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanita, 00161 Rome, Italy. michele.signore@iss.it. FAU - Veneroni, Silvia AU - Veneroni S AD - DOSMM, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy. silvia.veneroni@istitutotumori.mi.it. FAU - Cho, William Chi-Shing AU - Cho WC AD - Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China. chocs@ha.org.hk. FAU - Orlandi, Rosaria AU - Orlandi R AD - Molecular Targets Unit, Fondazione IRCCS Istituto Nazionale dei Tumouri, 20133 Milan, Italy. rosaria.orlandi@istitutotumori.mi.it. FAU - Verderio, Paolo AU - Verderio P AD - Unit of Medical Statistics, Biometry and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy. paolo.verderio@istitutotumori.mi.it. FAU - Bongarzone, Italia AU - Bongarzone I AD - Proteomics Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy. italia.bongarzone@istitutotumori.mi.it. LA - eng PT - Journal Article DEP - 20170214 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Biomarkers, Tumor) RN - 0 (Blood Proteins) RN - 0 (Hepcidins) RN - 0 (Interleukin-6) RN - 0 (Proteins) RN - 0 (Receptors, Transferrin) RN - 11096-26-7 (Erythropoietin) RN - 9007-73-2 (Ferritins) RN - E1UOL152H7 (Iron) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - *Biomarkers, Tumor MH - Blood Proteins MH - Breast Neoplasms/*diagnosis/genetics/*metabolism MH - Diagnosis, Differential MH - Enzyme-Linked Immunosorbent Assay MH - Erythropoietin/blood MH - Female MH - Ferritins/metabolism MH - Hepcidins/metabolism MH - Humans MH - Interleukin-6/blood MH - Iron/*metabolism MH - Middle Aged MH - Protein Array Analysis MH - Proteins/genetics/*metabolism MH - Receptors, Transferrin/metabolism MH - Young Adult PMC - PMC5343944 OTO - NOTNLM OT - Iron OT - STAT5 OT - breast cancer OT - ferroportin OT - hepcidin OT - iron chelators OT - metabolism OT - reverse phase protein array OT - transferrin receptor (TFR) COIS- The authors declare no conflict of interest. EDAT- 2017/02/22 06:00 MHDA- 2017/04/30 06:00 PMCR- 2017/02/01 CRDT- 2017/02/21 06:00 PHST- 2016/12/19 00:00 [received] PHST- 2017/02/01 00:00 [revised] PHST- 2017/02/06 00:00 [accepted] PHST- 2017/02/21 06:00 [entrez] PHST- 2017/02/22 06:00 [pubmed] PHST- 2017/04/30 06:00 [medline] PHST- 2017/02/01 00:00 [pmc-release] AID - ijms18020410 [pii] AID - ijms-18-00410 [pii] AID - 10.3390/ijms18020410 [doi] PST - epublish SO - Int J Mol Sci. 2017 Feb 14;18(2):410. doi: 10.3390/ijms18020410.