Breast Cancer Degradomic View Figure 2. The comparative base peak chromatograms of the BCP and HP peptidome components. Differences exist between the base peaks of the BCP and HP peptidome major components. doi:10.1371/journal.pone.0013133.g002 examples of the differential degradation in the BCP for tumor suppressors, e.g., ceruloplasmin [33], pigment epithelium-derived factor [34], and gelsolin [35], involved in angiogenesis, apoptosis, differentiation, Rac signaling, and mobility, etc. ApoA-IV, which has been reported having decreased blood concentration in cancer patients [36], is also high differentially degraded in the BCP examined (Figure 9D). Discussion The bottom-up proteomics results obtained in this study, generally with a detection limit of ,ng/mL [37], show that the blood proteome is not sensitive to the differences between the BCP and HP (Figure 1), and perhaps much more sensitive analytical technologies (e.g., with the detection limits of low level pg/mL) need to be explored for direct comparative blood proteomic studies, which is consistent with earlier insights [5]. In contrast, major changes in blood plasma degradome-peptidome are readily apparent for the BCP (see results shown in Figures 1, 2, 3, 4, 5, 6, 7, 8, 9). The degradomic information obtained in this work is also in agreement with characteristics known for breast cancer, suggesting that the broad top-down degradomic-peptidomic analysis has the potential to serve as an alternative strategy for discovery of the diagnostic and therapeutic targets for early detection of breast cancer. However, it is recognized that this work was limited to 15 BCP and the matched control HP samples. The observations at the present time does not allow statistical evaluation of the differential degradomic-peptidomic signatures, and extensive investigations of the degradomes-peptidomes of a much larger BCP population need to be explored to validate whether every BCP displays all or part of the degradomic features described in this work. The BCP tested in this work are for stages I, II and III (maybe spread to nearby lymph nodes but not distant parts of the body), but not for late (advanced) stage IV breast cancer; the differences between the different stages of breast cancer were not studied in this work. PLoS ONE | www.plosone.org 4 October 2010 | Volume 5 | Issue 10 | e13133