Impact of Protein Stability, Cellular Localization, and Abundance on Proteomic Detection of Tumor-Derived Proteins in Plasma

摘要: Tumor-derived, circulating proteins are potentially useful as biomarkers for detection of cancer, monitoring disease progression, regression and recurrence, assessment therapeutic response. Here we interrogated how a protein's stability, cellular localization, abundance affect its observability in blood by mass-spectrometry-based proteomics techniques. We performed proteomic profiling on tumors plasma from two different xenograft mouse models. A statistical analysis this data revealed protein properties indicative the level plasma. Though 20% identified were tumor-derived, only 5% observed tumor tissue found Both intracellular extracellular plasma; however, after normalizing abundance, seven times more likely to be detected. Although that abundant also plasma, relationship was nonlinear: Doubling spectral count increased rate 50%. Many secreted proteins, even those with relatively low count, but few observed. Proteins predicted stable dipeptide composition significantly than less proteins. The number tryptic peptides not related chance being Quantitative comparison large versus small measured associated size, one-to-one; 3-fold decrease size resulted 16-fold This study provides quantitative support tumor-derived marker prioritization strategy favors over all most