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Imagestream detection and characterisation of circulating tumour cells - a liquid biopsy for hepatocellular carcinoma?

Lookup NU author(s): Laura Ogle, Dr James Orr, Dr Catherine WilloughbyORCiD, Dr Claire Hutton, Professor Stuart McPhersonORCiD, Professor Ruth Plummer, Professor Nicola CurtinORCiD, Dr David Jamieson, Professor Helen ReevesORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Background The lack of progress in developing and delivering new therapies for hepatocellular carcinoma (HCC) is in part attributed to the risk related avoidance of tumour biopsy at diagnosis. Circulating tumour cells (CTCs) are a potential source of tumour tissue that could aid biological or biomarker research, treatment stratification and monitoring. Methods An imaging flow cytometry method, using immunofluorescence of cytokeratin, EpCAM, AFP, glypican-3 and DNA-PK together with analysis of size, morphology and DNA content, for detection of HCC CTCs was developed and applied to 69 patient and 31 control samples. The presence of CTCs as a prognostic indicator was assessed in multivariate analyses encompassing recognised prognostic parameters.Results Between 1 and 1642 CTCs were detected in blood samples from 45/69 HCC patients compared to 0/31 controls. CTCs positive for the epithelial markers cytokeratin and EpCAM were detected in 29% and 18% of patients respectively, while an additional 28% of patients had CTCs negative for all markers other than size and evidence of hyperploidy. CTC number correlated significantly with tumour size and portal vein thrombosis (PVT). The median survival of patients with >1 CTC was 7.5 months versus >34 months for patients with <1 CTC (p <0.001, Log rank), with significance retained in a multivariate analysis (HR 2.34, 95% CI 1.005-5.425, p=0.049) including tumour size and PVT.Conclusions The use of multiple parameters enhanced HCC CTC detection sensitivity, revealing biological associations and predictive biomarker potential that may be able to guide stratified medicine decisions and future research.

Publication metadata

Author(s): Ogle LF, Orr JG, Willoughby CE, Hutton C, McPherson S, Plummer R, Boddy AV, Curtin NC, Jamieson D, Reeves HL

Publication type: Article

Publication status: Published

Journal: Journal of Hepatology

Year: 2016

Volume: 65

Issue: 2

Pages: 305-313

Print publication date: 01/08/2016

Online publication date: 27/04/2016

Acceptance date: 14/04/2016

Date deposited: 14/06/2016

ISSN (print): 0168-8278

ISSN (electronic): 1600-0641

Publisher: Elsevier


DOI: 10.1016/j.jhep.2016.04.014


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Funder referenceFunder name
Cancer Research UK (CR UK)
Newcastle Experimental Cancer Medicine Center
Newcastle Medical School Faculty PhD Studentship
The Bobby Robson Foundation
HEALTH-F2-2009-241762European Community