Proteomic analysis of plasma exosomes in patients with metastatic colorectal cancer.

Background: The diagnosis and treatment of colorectal cancer (CRC), especially metastatic colorectal cancer (mCRC), is a major priority and research challenge. We screened for expression differences in the plasma exosomal proteomes of patients with mCRC, those with CRC, and healthy controls (HCs) to discover potential biomarkers for mCRC.

Methods: Plasma samples from five patients with mCRC, five patients with CRC, and five HCs were collected and processed to isolate exosomes by ultracentrifugation. Exosomal protein concentrations were determined using the BCA kit, and liquid chromatography-mass spectrometry was utilized to identify and analyze the proteins.

Results: From the exosomes isolated from plasma samples, a total of 994 quantifiable proteins were detected, including 287 differentially expressed proteins identified by quantitative proteomics analyses. Totals of 965, 963 and 968 proteins were identified in mCRC patients, CRC patients, and HCs, respectively. The study identified 83 proteins with differential expression in the plasma exosomes of mCRC patients. The top 10 upregulated proteins in the mCRC group and CRC groups were ITGA4, GNAI1, SFTPA2, UGGT1, GRN, LBP, SMIM1, BMP1, HMGN5, and MFAP4, while the top 10 downregulated proteins were PSMB8, LCK, RAB35, PSMB4, CD81, CD63, GLIPR2, RAP1B, RAB30, and CES1. Western Blot validation data confirmed that ITGA4 and GNAI1 were unequivocally enriched in plasma-derived exosomes from mCRC patients.

Conclusions: These differential proteins offer potential new candidate molecules for further research on the pathogenesis of mCRC and the identification of therapeutic targets. This study sheds light on the potential significance of plasma exosome proteomics studies in our understanding and treatment of mCRC.