Circulating Exosomal Proteins as New Diagnostic Biomarkers for Colorectal Cancer (EXOSCOL01): A Pilot Case-Controlled Study Focusing on MMP14 Potential.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. The French CRC screening campaign is based on fecal immunochemical tests (FIT), confirmed by colonoscopy, an invasive procedure with a poor participation rate. This study aimed to compare the expression of circulating exosomal proteins (MMP14, β1-Integrin subunit, β3-Integrin subunit, and α1(I) Collagen chain) in patients with CRC or adenomas. METHODS: A total of 71 patients were recruited, including 24 controls (normal colonoscopy), 11 patients with adenoma, and 36 with CRC. Plasmatic exosomal protein expression was measured by western blot analysis and reported to either protein or exosome content. RESULTS: The three groups were comparable regarding clinical characteristics. A significant difference was observed for MMP14 relative expression (p = 0.0007), MMP14 expression reported to exosomal protein content (p = 0.0003), and MMP14 expression reported to exosome content (p = 0.0005). These three parameters were significantly higher in patients with adenoma vs. control patients (p = 0.0013, p = 0.0004, and p = 0.0003, respectively). Only MMP14 relative intensity was significantly higher in the CRC group vs. the control group (p = 0.0018). CONCLUSIONS: Exosomal MMP14 is a promising early diagnostic biomarker for CRC and adenoma. These preliminary results warrant confirmation in larger studies using quantitative measurements such as ELISA or flow cytometry.