Development and application of mass spectrometry-based proteomics techniques to analyze human cancer tissue and serum plasma

Abstract

Biomarker expression in tissue or plasma can detect tumor or other disease in very early stages of its development and monitor the disease progression and also the effect of therapeutic interventions. Plasma is the favorite specimen sample source for biomarker from discovery to clinical practice because of its low invasive accessibility and reserve availability. Despite the great improvement of proteomic technologies, biomarker discovery in human plasma was restricted by the wide dynamic range in protein abundance with over ten orders of magnitude, results in low coverage of proteome. Without depletion of top 12 abundant proteins, we could only identify 224 proteins in single shot LC-MS/MS analysis. In order to detect low abundant proteins in plasma, we further used the MBR-based approach for quantifying the MS1 signals by the feature of match-between-runs (MBR) in MaxQuant. The number of identified proteins/peptides was increased to 1330/5948 with MBR using the reference peptides from Hela cells. In the future, we might be able to build the proteogenomics datasets by combining with individualized transcriptomics and genomics datasets from the individualized human plasma cohort.