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Published in: Hepatology International 4/2016

01-07-2016 | Original Article

An improved strategy to detect the epithelial-mesenchymal transition process in circulating tumor cells in hepatocellular carcinoma patients

Authors: Yong-kang Liu, Bao-shan Hu, Zhong-liang Li, Xu He, Yong Li, Li-gong Lu

Published in: Hepatology International | Issue 4/2016

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Abstract

Purpose

We adopted a new strategy to explore the relationship between the EMT process of CTCs and hepatocellular carcinoma (HCC). Furthermore, we intend to illustrate the potential diagnostic value of CTCs of distinct phenotypes in HCC.

Methods

The clinical data of 33 HCC patients and 10 healthy volunteers were collected retrospectively. By using the optimized CanPatrol CTC enrichment technique, patient blood samples of about 5 ml were collected, and CTCs were identified and characterized. The first step of this detection process was to isolate CTCs via a filter-based method; then, an RNA in situ hybridization (RNA-ISH) technique based on the branched DNA signal amplification technology was used to classify the CTCs according to EMT markers. The relationships between HCC CTCs and clinical characteristics were analyzed.

Results

The number of epithelial CTCs was related to tumor size (r = 0.456, p = 0.008), epithelial-mesenchymal-mixed CTCs were related to tumor number (r = 0.421, p = 0.015), and mesenchymal CTC was associated with metastasis (r = 0.375, p = 0.032). There was no significant correlation between CTC number and other clinicopathological factors, such as age, serum AFP level or cirrhosis.

Conclusions

Epithelial-mesenchymal-mixed CTCs seem to play an important role in EMT transition in HCC, mixed CTCs might be a vital factor for intrahepatic metastasis, and mesenchymal CTCs had the potential to be a predictor of extrahepatic metastasis.
Literature
1.
go back to reference Parkin DM, et al. Estimating the world cancer burden: Globocan 2000. Int J Cancer 2001;94(2):153–156CrossRefPubMed Parkin DM, et al. Estimating the world cancer burden: Globocan 2000. Int J Cancer 2001;94(2):153–156CrossRefPubMed
2.
go back to reference Ferenci P, et al. Hepatocellular carcinoma (HCC): a global perspective. J Clin Gastroenterol 2010;44(4):239–245.CrossRefPubMed Ferenci P, et al. Hepatocellular carcinoma (HCC): a global perspective. J Clin Gastroenterol 2010;44(4):239–245.CrossRefPubMed
3.
go back to reference Cabrera R, Nelson DR. Review article: the management of hepatocellular carcinoma. Aliment Pharmacol Ther 2010;31(4):461–476CrossRefPubMed Cabrera R, Nelson DR. Review article: the management of hepatocellular carcinoma. Aliment Pharmacol Ther 2010;31(4):461–476CrossRefPubMed
4.
5.
go back to reference Imamura H, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol 2003;38(2):200–207CrossRefPubMed Imamura H, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol 2003;38(2):200–207CrossRefPubMed
7.
go back to reference Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2002;2(6):442–54.CrossRefPubMed Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2002;2(6):442–54.CrossRefPubMed
10.
go back to reference Osta WA, et al. EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy. Cancer Res 2004;64(16):5818–5824CrossRefPubMed Osta WA, et al. EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy. Cancer Res 2004;64(16):5818–5824CrossRefPubMed
11.
go back to reference Giuliano M, et al. Circulating tumor cells as prognostic and predictive markers in metastatic breast cancer patients receiving first-line systemic treatment. Breast Cancer Res 2011;13(3):R67CrossRefPubMedPubMedCentral Giuliano M, et al. Circulating tumor cells as prognostic and predictive markers in metastatic breast cancer patients receiving first-line systemic treatment. Breast Cancer Res 2011;13(3):R67CrossRefPubMedPubMedCentral
12.
go back to reference Larsson A, et al. Increased cell proliferation and neurogenesis in the hippocampal dentate gyrus of old GFAP(−/−)Vim(−/−) mice. Neurochem Res 2004;29(11):2069–2073CrossRefPubMed Larsson A, et al. Increased cell proliferation and neurogenesis in the hippocampal dentate gyrus of old GFAP(−/−)Vim(−/−) mice. Neurochem Res 2004;29(11):2069–2073CrossRefPubMed
13.
go back to reference McInroy L, Maatta A. Down-regulation of vimentin expression inhibits carcinoma cell migration and adhesion. Biochem Biophys Res Commun 2007;360(1):109–114CrossRefPubMed McInroy L, Maatta A. Down-regulation of vimentin expression inhibits carcinoma cell migration and adhesion. Biochem Biophys Res Commun 2007;360(1):109–114CrossRefPubMed
14.
go back to reference Yu W, Kamara H, Svoboda KK. The role of twist during palate development. Dev Dyn 2008;237(10):2716–2725CrossRefPubMed Yu W, Kamara H, Svoboda KK. The role of twist during palate development. Dev Dyn 2008;237(10):2716–2725CrossRefPubMed
15.
go back to reference Paterlini-Brechot P, Benali NL. Circulating tumor cells (CTC) detection: clinical impact and future directions. Cancer Lett 2007;253(2):180–204CrossRefPubMed Paterlini-Brechot P, Benali NL. Circulating tumor cells (CTC) detection: clinical impact and future directions. Cancer Lett 2007;253(2):180–204CrossRefPubMed
16.
go back to reference Weissenstein U, et al. Detection of circulating tumor cells in blood of metastatic breast cancer patients using a combination of cytokeratin and EpCAM antibodies. BMC Cancer 2012;12:206CrossRefPubMedPubMedCentral Weissenstein U, et al. Detection of circulating tumor cells in blood of metastatic breast cancer patients using a combination of cytokeratin and EpCAM antibodies. BMC Cancer 2012;12:206CrossRefPubMedPubMedCentral
17.
go back to reference Deng G, et al. Enrichment with anti-cytokeratin alone or combined with anti-EpCAM antibodies significantly increases the sensitivity for circulating tumor cell detection in metastatic breast cancer patients. Breast Cancer Res 2008;10(4):R69CrossRefPubMedPubMedCentral Deng G, et al. Enrichment with anti-cytokeratin alone or combined with anti-EpCAM antibodies significantly increases the sensitivity for circulating tumor cell detection in metastatic breast cancer patients. Breast Cancer Res 2008;10(4):R69CrossRefPubMedPubMedCentral
18.
19.
20.
go back to reference Wu S, et al. Enrichment and enumeration of circulating tumor cells by efficient depletion of leukocyte fractions. Clin Chem Lab Med (CCLM) 2014;52(2):243–251CrossRef Wu S, et al. Enrichment and enumeration of circulating tumor cells by efficient depletion of leukocyte fractions. Clin Chem Lab Med (CCLM) 2014;52(2):243–251CrossRef
21.
go back to reference Zhang Y, et al. Circulating tumor cells in hepatocellular carcinoma: detection techniques, clinical implications, and future perspectives. Semin Oncol 2012;39(4):449–460CrossRefPubMed Zhang Y, et al. Circulating tumor cells in hepatocellular carcinoma: detection techniques, clinical implications, and future perspectives. Semin Oncol 2012;39(4):449–460CrossRefPubMed
22.
go back to reference Talasaz AH, et al. Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device. Proc Natl Acad Sci USA 2009;106(10):3970–3975CrossRefPubMedPubMedCentral Talasaz AH, et al. Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device. Proc Natl Acad Sci USA 2009;106(10):3970–3975CrossRefPubMedPubMedCentral
23.
go back to reference Andreopoulou E, et al. Comparison of assay methods for detection of circulating tumor cells in metastatic breast cancer: AdnaGen AdnaTest BreastCancer Select/Detect versus Veridex Cell Search system. Int J Cancer 2012;130(7):1590–1597CrossRefPubMed Andreopoulou E, et al. Comparison of assay methods for detection of circulating tumor cells in metastatic breast cancer: AdnaGen AdnaTest BreastCancer Select/Detect versus Veridex Cell Search system. Int J Cancer 2012;130(7):1590–1597CrossRefPubMed
24.
go back to reference Miller MC, Doyle GV, Terstappen LW. Significance of circulating tumor cells detected by the cell search system in patients with metastatic breast colorectal and prostate cancer. J Oncol 2010;2010:617421CrossRefPubMed Miller MC, Doyle GV, Terstappen LW. Significance of circulating tumor cells detected by the cell search system in patients with metastatic breast colorectal and prostate cancer. J Oncol 2010;2010:617421CrossRefPubMed
25.
go back to reference Sun YF, et al. Circulating stem cell-like epithelial cell adhesion molecule-positive tumor cells indicate poor prognosis of hepatocellular carcinoma after curative resection. Hepatology 2013;57(4):1458–1468CrossRefPubMed Sun YF, et al. Circulating stem cell-like epithelial cell adhesion molecule-positive tumor cells indicate poor prognosis of hepatocellular carcinoma after curative resection. Hepatology 2013;57(4):1458–1468CrossRefPubMed
26.
go back to reference Allard WJ, et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 2004;10(20):6897–6904CrossRefPubMed Allard WJ, et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 2004;10(20):6897–6904CrossRefPubMed
27.
go back to reference Cristofanilli M, et al. Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 23(7):1420–1430CrossRefPubMed Cristofanilli M, et al. Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 23(7):1420–1430CrossRefPubMed
28.
go back to reference Matthew EM, et al. A multiplexed marker-based algorithm for diagnosis of carcinoma of unknown primary using circulating tumor cells. Oncotarget 2016;7(4):3662–3676PubMed Matthew EM, et al. A multiplexed marker-based algorithm for diagnosis of carcinoma of unknown primary using circulating tumor cells. Oncotarget 2016;7(4):3662–3676PubMed
30.
Metadata
Title
An improved strategy to detect the epithelial-mesenchymal transition process in circulating tumor cells in hepatocellular carcinoma patients
Authors
Yong-kang Liu
Bao-shan Hu
Zhong-liang Li
Xu He
Yong Li
Li-gong Lu
Publication date
01-07-2016
Publisher
Springer India
Published in
Hepatology International / Issue 4/2016
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-016-9732-7

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