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Clin Proteomics. 2015 Mar 21;12(1):8. doi: 10.1186/s12014-015-9080-y. eCollection 2015.

Proteomics profiling identify CAPS as a potential predictive marker of tamoxifen resistance in estrogen receptor positive breast cancer.

Author information

1
Department Oncology-Pathology, Cancer Proteomics Mass spectrometry, Science for Life Laboratory, Karolinska Institutet, SE-171 65 Stockholm, Sweden.
2
Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
3
Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden ; Regional cancer center Southeast Sweden, County Council of Östergötland, Linköping, Sweden.
4
Department of Oncology, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden.
5
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, Stockholm, 17177 Sweden.
6
Department Oncology-Pathology, Cancer Proteomics Mass spectrometry, Science for Life Laboratory, Karolinska Institutet, SE-171 65 Stockholm, Sweden ; Department of Oncology, Sahlgrenska Academy and University Hospital, SE-413 45 Gothenburg, Sweden.

Abstract

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.

KEYWORDS:

CAPS; Calcyphosine; Endocrine resistance; Estrogen receptor; MX1; Proteomics; Receptor-positive breast cancer

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