Vasodilator-stimulated phosphoprotein acts as a potential plasma-derived exosomal protein marker for early detection of colorectal cancer

Colorectal cancer (CRC) has the third most common cancer incidence and the second most frequent cause of cancer death worldwide, with greater mortality rate when detected at advanced stages. The earlier the cancer is detected, the better the chance of survival. Colonoscopy is currently the gold standard for CRC diagnosis but is invasive and costly. Therefore, there is a pressing need for a highly sensitive, specific, and minimally invasive biomarker for the detection of CRC at asymptotic stages. This study aims to identify blood-borne exosomal protein markers for the early detection of high-risk adenoma and CRC. Proteomics data (LC-MS/MS) were collected on plasma-derived exosomes from Normal (N), Low-risk adenoma (LRA), High-risk adenoma (HRA), and Colorectal cancer (CRC) groups. We found 16 exosomal proteins significantly upregulated in the HRA or CRC group compared to the N or LRA group. Validation of P-selectin (LYAM3, Log2FC -2.50, p-value 0.039), vasodilator-stimulated phosphoprotein (VASP, Log2FC -1.75, p-value 0.001), and Multimerin-1 (MMRN1, Log2FC -0.93, p-value 0.006) as potential biomarkers for high-risk adenomas and CRC was performed using Western blot analysis in plasma-derived exosomes extracted from individual samples. VASP was significantly more abundant in high-risk adenoma or CRC samples than in low-risk adenoma or healthy controls, indicating that VASP could distinguish the high-risk adenoma or CRC groups from the low-risk adenoma or healthy controls. We therefore conclude that VASP can potentially act as a blood-based exosomal protein marker for the early detection of high-risk adenomas and CRC.