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Proteomics profiling identify CAPS as a potential predictive marker of tamoxifen resistance in estrogen receptor positive breast cancer
Department Oncology-Pathology, Cancer Proteomics Mass spectrometry, Science for Life Laboratory, Karolinska Institutet, SE-171 65 Stockholm, Sweden.
Department Oncology-Pathology, Cancer Proteomics Mass spectrometry, Science for Life Laboratory, Karolinska Institutet, SE-171 65 Stockholm, Sweden.
Department Oncology-Pathology, Cancer Proteomics Mass spectrometry, Science for Life Laboratory, Karolinska Institutet, SE-171 65 Stockholm, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Health Sciences.
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2015 (English)In: Clinical Proteomics, ISSN 1542-6416, E-ISSN 1559-0275, Vol. 12, no 1, 8- p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Despite the success of tamoxifen since its introduction, about one-third of patients with estrogen (ER) and/or progesterone receptor (PgR) - positive breast cancer (BC) do not benefit from therapy. Here, we aim to identify molecular mechanisms and protein biomarkers involved in tamoxifen resistance.

RESULTS: Using iTRAQ and Immobilized pH gradient-isoelectric focusing (IPG-IEF) mass spectrometry based proteomics we compared tumors from 12 patients with early relapses (<2 years) and 12 responsive to therapy (relapse-free > 7 years). A panel of 13 proteins (TCEAL4, AZGP1, S100A10, ALDH6A1, AHNAK, FBP1, S100A4, HSP90AB1, PDXK, GFPT1, RAB21, MX1, CAPS) from the 3101 identified proteins, potentially separate relapse from non-relapse BC patients. The proteins in the panel are involved in processes such as calcium (Ca(2+)) signaling, metabolism, epithelial mesenchymal transition (EMT), metastasis and invasion. Validation of the highest expressed proteins in the relapse group identify high tumor levels of CAPS as predictive of tamoxifen response in a patient cohort receiving tamoxifen as only adjuvant therapy.

CONCLUSIONS: This data implicate CAPS in tamoxifen resistance and as a potential predictive marker.

Place, publisher, year, edition, pages
2015. Vol. 12, no 1, 8- p.
Keyword [en]
CAPS; Calcyphosine; Endocrine resistance; Estrogen receptor; MX1; Proteomics; Receptor-positive breast cancer
National Category
Cancer and Oncology Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-125931DOI: 10.1186/s12014-015-9080-yPubMedID: 25878567OAI: oai:DiVA.org:liu-125931DiVA: diva2:910424
Available from: 2016-03-09 Created: 2016-03-09 Last updated: 2016-03-31

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Stål, OlleFohlin, Helena
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Division of Clinical SciencesDepartment of OncologyFaculty of Health SciencesRegional Cancer Center South East Sweden
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