Cancer-associated circulating large extracellular vesicles in cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC)

Abstract

Background: Here, we assess the diagnostic value of tumour-associated microparticles (taMPs), for the detection and therapy monitoring of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Methods: FACS was applied to detect various taMP populations in patients’ sera that were associated with the presence of a liver tumour. In total 172 patients with liver cancer, 54 with cirrhosis and no liver neoplasia, 202 control subjects were enrolled and in 27 liver cancer patients a R0 resection was performed. Results: AnnexinV+EpCAM+ASGPR1+CD133+ taMPs allowed the distinction of liver malignancies and cirrhosis from tumour-free individuals and, more importantly, from patients carrying other non-liver cancers. AnnexinV+EpCAM+ASGPR1+ taMPs were increased in liver cancer-bearing patients (HCC orCCA) by 3.05-fold (p< 0.0005). ROC values, sensitivity/specificity and positive/negative predictive values ( >78%) indicated a potent diagnostic accuracy. In addition, AnnexinV+EpCAM+ASGPR1+ taMPs decreased from 26.7 (pre-R0 resection) to 16.1 AnnexinV+EpCAM+ASGPR1+ taMPs per 103 AnnexinV+ MPs (day 2 post-R0 resection, p<0.005), and remained low at day 10 post-OP (7.7, p<0.05). The smallest size of successfully detected liver tumours were ranging between 11-15 mm. Conclusion: Our results demonstrate that taMPs-based liquid biopsy might represents a novel accurate tool that will improve diagnostics and therapy in patients with primary liver cancers. Additionally, taMPs could be suitable to monitor anti-tumoral therapy response.