Circulating Exosomes proteome of Colorectal Cancer Based on Rapid DIA-MS

ABSTRACT: Early screening is essential for the treatment of colorectal cancer (CRC). Concerns are rising regarding liquid biopsy due to its low invasiveness and reproducibility, especially when tissue samples are not available. Recent reports suggest that tumor-specific proteins may be stably expressed in exosomes. Here we isolated exosomes from the plasma of CRC patients from different stages by prolonged ultracentrifugation combined with sucrose density gradient centrifugation. We performed proteomics and phosphoproteomics analysis of these exosomes using TMT-labeled LC-MS/MS, and found that fibronectin 1(FN1), haptoglobin (HP), S100A9, fibrinogen α chain (FGA) and their phosphorylation levels associated significantly with tumor progression. After verified this result by western blot (WB) in both another cohort and in mouse subcutaneous tumor model, we confirmed the difference among healthy individuals and patients diagnosed with colon adenoma or CRC by optimized Data Independent Acquisition (DIA) mass spectrometry. Our data suggest that rapid DIA mass spectrometry-based liquid biopsy of FGA+ circulating exosomes (crExos) could serve as a potential non-invasive diagnostic and screening tool to identify early stages of CRC.

ORGANISM(S): Homo Sapiens

SUBMITTER: Shu Zheng  

PROVIDER: PXD015921 | iProX | Sun Oct 20 00:00:00 BST 2019

REPOSITORIES: iProX