Background & Aims
Large extracellular vesicles, specifically AnnexinV+ EpCAM+ CD147+ tumour-associated microparticles (taMPs), facilitate the detection of colorectal
carcinoma (CRC), non-small cell lung carcinoma (NSCLC) as well as pancreas carcinoma
(PaCa). Here we assess the diagnostic value of taMPs for detection and monitoring
of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Specifically, the
aim of this study was to differentiate liver taMPs from other cancer taMPs, such as
CRC and NSCLC.
Methods
Fluorescence-activated cell scanning (FACS) was applied to detect various taMP populations
in patients’ sera that were associated with the presence of a tumour (AnnexinV+ EpCAM+ CD147+ taMPs) or could discriminate between cirrhosis (due to HCV or HBV) and liver cancers
(AnnexinV+ EpCAM+ ASGPR1+ taMPs). In total 172 patients with liver cancer (HCC or CCA), 54 with cirrhosis and
no liver neoplasia, and 202 control subjects were enrolled.
Results
The results indicate that AnnexinV+ EpCAM+ CD147+ taMPs were elevated in HCC and CCA. Furthermore, AnnexinV+ EpCAM+ ASGPR1+ CD133+ taMPs allowed the distinction of liver malignancies (HCC or CCA) and cirrhosis from
tumour-free individuals and, more importantly, from patients carrying other non-liver
cancers. In addition, AnnexinV+ EpCAM+ ASGPR1+ taMPs were increased in liver cancer-bearing patients compared to patients with cirrhosis
that lacked any detectable liver malignancy. The smallest sizes of successfully detected
cancers were ranging between 11–15 mm. AnnexinV+ EpCAM+ ASGPR1+ taMPs decreased at 7 days after curative R0 tumour resection suggesting close correlations with tumour
presence. ROC values, sensitivity/specificity scores and positive/negative predictive
values (>78%) indicated a potent diagnostic accuracy of AnnexinV+ EpCAM+ ASGPR1+ taMPs.
Conclusion
These data provide strong evidence that AnnexinV+ EpCAM+ ASGPR1+ taMPs are a novel biomarker of HCC and CCA liquid biopsy that permit a non-invasive
assessment of the presence and possible extent of these cancers in patients with advanced
liver diseases.
Lay summary
Microparticles (MPs) are small vesicles that bleb from the membrane of every cell,
including cancer cells, and are released to circulate in the bloodstream. Since their
surface composition is similar to the surface of their underlying parental cell, MPs
from the bloodstream can be isolated and by screening their surface components, the
presence of their parental cells can be identified. This way, it was possible to detect
and discriminate between patients bearing liver cancer and chronic liver cirrhosis.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: March 04, 2017
Accepted:
February 23,
2017
Received in revised form:
February 22,
2017
Received:
January 16,
2017
Identification
Copyright
© 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
