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

蛋白质组学分析表明 CAPS 是雌激素受体阳性乳腺癌他莫昔芬耐药性的潜在预测标志物

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作者:Henrik J Johansson, Betzabe C Sanchez, Jenny Forshed, Olle Stål, Helena Fohlin, Rolf Lewensohn, Per Hall, Jonas Bergh, Janne Lehtiö, Barbro K Linderholm

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

Conclusions

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

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.

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