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

Clinical Proteomics

Barbro K Linderholm⁵  Betzabe C Sanchez⁴  Rolf Lewensohn⁶  Henrik J Johansson⁴  Jenny Forshed⁴  Olle Stål²  Jonas Bergh⁴  Per Hall¹  Helena Fohlin³  Janne Lehtiö⁴ 

[1] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SwedenDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SwedenDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden;Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, SwedenDepartment of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, SwedenDepartment of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden;Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, SwedenRegional cancer center Southeast Sweden, County Council of Östergötland, Linköping, SwedenDepartment of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, SwedenDepartment of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, SwedenRegional cancer center Southeast Sweden, County Council of Östergötland, Linköping, SwedenRegional cancer center Southeast Sweden, County Council of Östergötland, Linköping, SwedenDepartment of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, SwedenRegional cancer center Southeast Sweden, County Council of Östergötland, Linköping, Sweden;Department Oncology-Pathology, Cancer Proteomics Mass spectrometry, Science for Life Laboratory, Karolinska Institutet, Stockholm, SwedenDepartment Oncology-Pathology, Cancer Proteomics Mass spectrometry, Science for Life Laboratory, Karolinska Institutet, Stockholm, SwedenDepartment Oncology-Pathology, Cancer Proteomics Mass spectrometry, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden;Department Oncology-Pathology, Cancer Proteomics Mass spectrometry, Science for Life Laboratory, Karolinska Institutet, Stockholm, SwedenDepartment of Oncology, Sahlgrenska Academy and University Hospital, Gothenburg, SwedenDepartment Oncology-Pathology, Cancer Proteomics Mass spectrometry, Science for Life Laboratory, Karolinska Institutet, Stockholm, SwedenDepartment Oncology-Pathology, Cancer Proteomics Mass spectrometry, Science for Life Laboratory, Karolinska Institutet, Stockholm, SwedenDepartment of Oncology, Sahlgrenska Academy and University Hospital, Gothenburg, SwedenDepartment of Oncology, Sahlgrenska Academy and University Hospital, Gothenburg, SwedenDepartment Oncology-Pathology, Cancer Proteomics Mass spectrometry, Science for Life Laboratory, Karolinska Institutet, Stockholm, SwedenDepartment of Oncology, Sahlgrenska Academy and University Hospital, Gothenburg, Sweden;Department of Oncology, Radiumhemmet, Karolinska University Hospital, Stockholm, SwedenDepartment of Oncology, Radiumhemmet, Karolinska University Hospital, Stockholm, SwedenDepartment of Oncology, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden

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

DOI  :  10.1186/s12014-015-9080-y

来源: Humana Press Inc

【 摘 要 】

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 (Ca²⁺) 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.

【 授权许可】

Unknown