Identification of CD147-positive extracellular vesicles as novel non-invasive biomarkers for the diagnosis and prognosis of colorectal cancer

Abstract

BackgroundThe mortality rate of colorectal cancer (CRC) can be decreased with effective screening and early diagnosis. Exosomes are released from cancer cells into the bloodstream, and circulating exosomes may serve as novel biomarkers. This study aimed to identify a sensitive and rapid method of exosome collection and measurement using specific antibodies. MethodsExoCounter, a high-sensitive exosome-counting system, allows the identification of exosomes without enrichment or purification, based on the identification of the transmembrane protein—CD147—on serum exosomes that are associated with CRC. ResultsReceiver operating characteristic curves between healthy donors and CRC patients were described and assessed by CD147-specific exosomes (exo-CD147), CEA, and CA19-9. And area under curves for exo-CD147, CEA, and CA19-9 were 0.827 (95%CI: 0.764–0.891), 0.630 (95%CI: 0.536–0.724), and 0.659 (95%CI: 0.559–0.759), respectively. Drawing a clinical decision curve of exo-CD147 for the diagnosis of CRC metastases showed that when the threshold probability of exo-CD147 was between 20% and 92%, the net clinical utilization rate was higher than for all patients with or without metastases. A nomogram was constructed using multivariate COX regression analysis to select significant variables such as the high CD147 group (>34 × 105 particles). Calibration curves for 1-, 3-, and 5-year survival rates of CRC patients showed that the actual 1-, 3-, and 5-year survival rates were in excellent agreement with the survival rates predicted by the nomogram. ConclusionsThe increased CD147 expression in exosomes could serve as a diagnostic and prognostic biomarker for CRC.