Potential Prognostic Value of Exosomal BP1 in Breast Cancer
Open AccessBeta protein 1 (BP1) is an isoform protein of the DLX4 gene that is a member of the homeobox gene family. Previous work showed BP1 was activated in 80% of invasive ductal breast (IDC) tumors, where 100% of estrogen receptor (ER) negative tumors and 73% of ER positive tumors were BP1 positive. Moreover, the intensity of BP1 levels was associated with tumor cell survival, breast cancer aggressiveness and metastasis. It was also observed that BP1 protein could be released from tumor cell lines via small membrane- bound vesicles called exosomes. In addition, exosomal proteins have shown their unique characteristics compared to traditional biomarkers for carcinoma diagnosis and prognosis in previous research. Therefore, we hypothesized that analysis of serum exosomal BP1 protein may provide a novel biomarker for diagnosis or prognosis of breast cancer.Exosomes were isolated from serum of women with metastatic breast cancer and normal controls using the commercially available Exosome Precipitation Solution. In addition, three different antibodies targeting the different peptides of BP1 were designed to find the most effective BP1 protein antibody to be used in this project. Then, entire exosomal protein levels in serum were analyzed using BCA assay and exosomal BP1 protein levels were determined using Western blot. In order to develop a method that could be easily used in the clinic, an ELISA assay was also designed to assess the exosomal BP1 protein concentrations in the serum from metastatic breast cancer patients and normal controls.It was observed that the entire exosomal protein levels have no significant differences between that in breast cancer patients and in controls while the higher-grade breast cancer patients tend to have more exosomal proteins. The results of Western blot and ELISA both showed that exosomal BP1 protein levels were significantly higher in the breast cancer samples compared to normal controls (P < 0.05). Moreover, Western blot results suggested that the ER positive patients have much more (P < 0.05) exosomal BP1 protein in the serum compared to ER negative groups.In this study, it was showed for the first time that BP1 protein is exosomally packaged in the breast cancer patients’ serum. The significant difference in the exosomal BP1 protein levels between the serum from women with metastatic breast cancer and that from normal controls indicated that exosomal BP1 protein in the serum could be a potential prognostic biomarker for breast cancer. Furthermore, the ELISA assay designed to be easily used for exosomal BP1 protein quantification may have many uses in the clinic through aiding in prognosis, monitoring therapy and early detection.
- All rights reserved
Notice to Authors
If you are the author of this work and you have any questions about the information on this page, please use the Contact form to get in touch with us.