Imagestream detection and characterisation of circulating tumour cells – A liquid biopsy for hepatocellular carcinoma?
[Display omitted] 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...
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| Veröffentlicht in: | Journal of hepatology Jg. 65; H. 2; S. 305 - 313 |
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| Format: | Journal Article |
| Sprache: | Englisch |
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Elsevier B.V
01.08.2016
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| ISSN: | 0168-8278, 1600-0641 |
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| Abstract | [Display omitted]
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.
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.
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 7.5months versus >34months 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.
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.
Characteristics of tumour tissues can be used to predict outcomes for individual patients with cancer, as well as help to choose their best treatment. Biopsy of liver cancers carries risks, however, and is usually avoided. Some cancer cells enter the blood, and although they are very rare, we have developed a method of finding and characterising them in patients with liver cancer, which we hope will provide a low risk means of guiding treatment. |
|---|---|
| AbstractList | [Display omitted]
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.
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.
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 7.5months versus >34months 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.
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.
Characteristics of tumour tissues can be used to predict outcomes for individual patients with cancer, as well as help to choose their best treatment. Biopsy of liver cancers carries risks, however, and is usually avoided. Some cancer cells enter the blood, and although they are very rare, we have developed a method of finding and characterising them in patients with liver cancer, which we hope will provide a low risk means of guiding treatment. 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. 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. 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 7.5months versus >34months 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. 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. Characteristics of tumour tissues can be used to predict outcomes for individual patients with cancer, as well as help to choose their best treatment. Biopsy of liver cancers carries risks, however, and is usually avoided. Some cancer cells enter the blood, and although they are very rare, we have developed a method of finding and characterising them in patients with liver cancer, which we hope will provide a low risk means of guiding treatment. BACKGROUND & AIMSThe 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.METHODSAn 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.RESULTSBetween 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 7.5months versus >34months 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.CONCLUSIONSThe 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.LAY SUMMARYCharacteristics of tumour tissues can be used to predict outcomes for individual patients with cancer, as well as help to choose their best treatment. Biopsy of liver cancers carries risks, however, and is usually avoided. Some cancer cells enter the blood, and although they are very rare, we have developed a method of finding and characterising them in patients with liver cancer, which we hope will provide a low risk means of guiding treatment. Graphical abstract |
| Author | Willoughby, Catherine E. Orr, James G. McPherson, Stuart Boddy, Alan V. Curtin, Nicola J. Hutton, Claire Reeves, Helen L. Jamieson, David Ogle, Laura F. Plummer, Ruth |
| Author_xml | – sequence: 1 givenname: Laura F. surname: Ogle fullname: Ogle, Laura F. organization: Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK – sequence: 2 givenname: James G. surname: Orr fullname: Orr, James G. organization: The Liver Group, Department of Medicine, Freeman Hospital, Newcastle-upon-Tyne Hospitals, NHS Foundation Trust, UK – sequence: 3 givenname: Catherine E. surname: Willoughby fullname: Willoughby, Catherine E. organization: Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK – sequence: 4 givenname: Claire surname: Hutton fullname: Hutton, Claire organization: Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK – sequence: 5 givenname: Stuart surname: McPherson fullname: McPherson, Stuart organization: The Liver Group, Department of Medicine, Freeman Hospital, Newcastle-upon-Tyne Hospitals, NHS Foundation Trust, UK – sequence: 6 givenname: Ruth surname: Plummer fullname: Plummer, Ruth organization: Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK – sequence: 7 givenname: Alan V. surname: Boddy fullname: Boddy, Alan V. organization: Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK – sequence: 8 givenname: Nicola J. surname: Curtin fullname: Curtin, Nicola J. organization: Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK – sequence: 9 givenname: David surname: Jamieson fullname: Jamieson, David email: david.jamieson@ncl.ac.uk organization: Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK – sequence: 10 givenname: Helen L. surname: Reeves fullname: Reeves, Helen L. organization: Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27132171$$D View this record in MEDLINE/PubMed |
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| Copyright | 2016 European Association for the Study of the Liver European Association for the Study of the Liver Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. |
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| Keywords | EHD T2DM NAFLD EpCAM ImageStream HR AFP PVT PBC TTP EASL ECOG Circulating tumour cells WBC Liquid biopsy CTCs BMI AIH DNA-PK DEB-TACE RBCs EORTC BCLC CK HCC GPC-3 ASGPR PST ARLD Biomarkers CLD ISET SIRT Hepatocellular cancer red blood cells asiaglycoprotein receptor time to progression glypican-3 circulating tumour cells cytokeratin drug eluting bead-transarterial chemoembolization alphafetoprotein white blood cells primary biliary cirrhosis chronic liver disease performance status extra-hepatic disease Barcelona clinic liver cancer body mass index European association for the study of the liver European organisation for research and treatment of cancer portal vein thrombosis hepatocellular cancer epithelial cell adhesion molecule non-alcoholic fatty liver disease selective internal radiation therapy alcohol related liver disease Eastern cooperative oncology group autoimmune hepatitis type 2 diabetes mellitus isolation by size of epithelial cell hazard ratio DNA-dependent kinase |
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The lack of progress in developing and delivering new therapies for hepatocellular carcinoma (HCC) is in part attributed to the risk related... Graphical abstract The lack of progress in developing and delivering new therapies for hepatocellular carcinoma (HCC) is in part attributed to the risk related avoidance of... BACKGROUND & AIMSThe lack of progress in developing and delivering new therapies for hepatocellular carcinoma (HCC) is in part attributed to the risk related... |
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| SubjectTerms | Biomarkers Biomarkers, Tumor Carcinoma, Hepatocellular Circulating tumour cells Gastroenterology and Hepatology Hepatocellular cancer Humans ImageStream Liquid Biopsy Liver Neoplasms Neoplastic Cells, Circulating |
| Title | Imagestream detection and characterisation of circulating tumour cells – A liquid biopsy for hepatocellular carcinoma? |
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