Blood peptidome-degradome profile of breast cancer.
BACKGROUND
Cancer 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.


RESULTS
The 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.


CONCLUSIONS
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.
Shen
Yufeng
Y
Biological Science Division, Pacific Northwest National Laboratory, Richland, Washington, United States of America. Yufeng.shen@pnl.gov
Tolić
Nikola
N
Liu
Tao
T
Zhao
Rui
R
Petritis
Brianne O
BO
Gritsenko
Marina A
MA
Camp
David G
DG
Moore
Ronald J
RJ
Purvine
Samuel O
SO
Esteva
Francisco J
FJ
Smith
Richard D
RD
D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000097:blood*; D005260:Female; D005583:Fourier Analysis; D006801:Humans; D006868:Hydrolysis; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000097:blood*; D010455:Peptides / Q000737:chemistry*; D020543:Proteome
D009363:Neoplasm Proteins; D010455:Peptides; D020543:Proteome