SPOD2 Microvesicles as biomarkers for the screening of colorectal neoplasm

Abstract Background Colorectal cancer (CRC) is the second cause of cancer death worldwide. Screening for CRC by Faecal Immunochemical Test (FIT) aims to detect early cases before symptoms occur. Yet, the FIT has poor predictive value and low compliance rate. To address this, the role of circulating microvesicles as potential screening tool is a novel approach that warrants prioritised research. Methods In a two-gate diagnostic accuracy study, 35 patients with benign colorectal polyps (BCRP) (n=16) and colorectal cancer (CRC) (n=19) were compared to 17 age-matched healthy controls. Total annexin-V positive microvesicles and sub-populations positive for selected biomarkers relevant to bowel neoplasm were evaluated in patients’ plasma using flow cytometry. Results Total plasma microvesicles, and sub-populations positive for CD31, CD42a, CD31+/CD42a-, EPHB2, ICAM and LGR5 (component factor-1) were able to identify patients with BCRP and CRC with a receiver operator curve (AUC) accuracy of a 100% (95% CI: 100% to 100%) and 95% (95% CI: 88% to 100%) respectively. To identify patients with BCRP, a cut-off point value of component factor-1 ≥761 microvesicles/µL demonstrated a 100% sensitivity, specificity and negative predictive value (NPV) and a 93% positive predictive value (PPV). To identify patients with CRC, a cut-off value of component factor-1 ≥439 microvesicles/µL demonstrated a 100% sensitivity, specificity and NPV and a 65% PPV. CEA+ microvesicles sub-population were significantly (p<0.02) higher in CRC in comparison to BCRP. Conclusion Microvesicles as biomarkers for the early detection of CRC is a simple and effective tool that yields a potential breakthrough in clinical management.