Evaluation of the Plasma Peptidome and Its Correlation to the Tumor Proteome Evaluation of the Plasma Peptidome and Its Correlation to the Tumor Proteome Plasma is a widely accepted and readily available body fluid used for detection and monitoring of various diseases. However, it is also a highly complex mixture of proteins, peptides, sugars and lipids that spans over 7 logs in concentration. These highly abundant proteins obscure the identification of smaller molecules that are less abundant in plasma, some of which may be of biological interest. We developed a novel technique to eliminate highly abundant proteins to examine the low molecular weight fraction of plasma (peptidome) and found that it is a rich, but so far untapped source of biomarkers. Examining the plasma peptidome, while less diverse than the whole plasma proteome, is a simple technique that can be performed rapidly (30 to 60 minutes per sample). Many high profile groups are focused on depletion of highly abundant proteins in plasma that are high molecular weight. This is time-consuming, inefficient and expensive. Fractionation of plasma by molecular weight simplifies the material for LC separation followed by MS/MS analysis allowing greater resolution and depth of the peptide content in plasma than other methods. Evidence that we can work backwards from the plasma proteome/peptidome-to a tumor proteome is as follows. While performing mass spectrometry (LC-MS/MS) on plasma from pancreas cancer patients, we noticed that fragments from two proteins were found very frequently in pancreas cancer patient plasma. We found them in 19 of 21 patients with a surgical and pathological diagnosis of ductal adenocarcinoma (DA). Neither of these two proteins or protein fragments were ever found in plasma from 42 normal donors using the same methods. These proteins are QSOX1 and SerpinF2. QSOX1 has been implicated in inhibition of apoptosis due oxidative stress, but has also been reported to be expressed when fibroblasts become quiescent. The other protein was identified as SerpinF2 (alpha 2-antiplasmin), the main inhibitor of plasmin and fibrinolytic activity. SerpinF2 has been suggested to be involved in invasion of tumor cells through basement membranes resulting in metastasis.
|Effective start/end date||3/1/09 → 8/31/11|
- Translational Genomics Research Institute (TGen): $235,319.00
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