Abstract
BackgroundCancer invasion and metastasis are closely associated with activities within the degradome; however, little is known about whether these activities can be detected in the blood of cancer patients.Methodology and Principal FindingsThe peptidome-degradome profiles of pooled blood plasma sampled from 15 breast cancer patients (BCP) and age, race, and menopausal status matched control healthy persons (HP) were globally characterized using advanced comprehensive separations combined with tandem Fourier transform mass spectrometry and new data analysis approaches that facilitated top-down peptidomic analysis. The BCP pool displayed 71 degradome protein substrates that encompassed 839 distinct peptidome peptides. In contrast, the HP 50 degradome substrates found encompassed 425 peptides. We find that the ratios of the peptidome peptide relative abundances can vary as much as >4000 fold between BCP and HP. The experimental results also show differential degradation of substrates in the BCP sample in their functional domains, including the proteolytic and inhibitory sites of the plasmin-antiplasmin and thrombin-antithrombin systems, the main chains of the extracellular matrix protection proteins, the excessive degradation of innate immune system key convertases and membrane attack complex components, as well as several other cancer suppressor proteins.ConclusionsDegradomics-peptidomics profiling of blood plasma is highly sensitive to changes not evidenced by conventional bottom-up proteomics and potentially provides unique signatures of possible diagnostic utility.
Highlights
Breast cancer is the most common malignancy in Western women; in 2009, more than 192,000 women were estimated to be diagnosed and,40,000 died of this disease in the United States alone [1]
Degradomics-peptidomics profiling of blood plasma is highly sensitive to changes not evidenced by conventional bottom-up proteomics and potentially provides unique signatures of possible diagnostic utility
Blood plasma samples for this work were collected under the identical lab protocol from15 breast cancer patients (BCP) (ER positive, Her2 negative; invasive ductal carcinoma; 5 are stage I, 7 are stage II and 3 are stage III) and 15 control healthy persons (HP) of matched age, race, and menopausal status
Summary
Breast cancer is the most common malignancy in Western women; in 2009, more than 192,000 women were estimated to be diagnosed and ,40,000 died of this disease in the United States alone [1]. Breast cancer is a heterogeneous disease, and prognosis is determined largely by tumor size, shape, location, and metastasis in addition to molecular characteristics, such as whether the tumor is hormone receptor-positive or -negative, genetic factors, and the rate of cell division [2]. The present results obtained for the samples carefully selected suggest that the breast cancer patients have increased degradation of functional domains of cancerrelevant proteins, including proteases and inhibitors, extracellular matrix (ECM)-relevant proteins, innate immune system key components, and other protein molecules functioning to suppress cancers. The present results support the view that the peptidome/degradome is a potentially rich source of makers, support the use of the present top-down proteomic analytical strategies for obtain of the relevant unique information, and highlight the need for more extensive degradomic-peptidomic studies of individual samples, as is enabled by the present work
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
