Epithelial-mesenchymal transition markers expressed in circulating tumor cells in hepatocellular carcinoma patients with different stages of disease

Autor: Li Jc, Zhou Z, Xin-Mei Huang, Li Huashun, Ping Liang, Zhao Hongwen, Huifeng Pi, Lu Zheng, Guohua Zuo, Li Yin, Shuangnian Xu, Ke-qiang Han, Zubin Yu
Rok vydání: 2013
Předmět:
Male
Cancer Research
Pathology
medicine.medical_specialty
Carcinoma
Hepatocellular
Epithelial-Mesenchymal Transition
Immunology
Asialoglycoproteins
Fluorescent Antibody Technique
Vimentin
Asialoglycoprotein Receptor
Cell Separation
circulating tumor cells
epithelial–mesenchymal transition
Metastasis
Flow cytometry
Cellular and Molecular Neuroscience
Circulating tumor cell
Cell Line
Tumor
medicine
Carcinoma
Biomarkers
Tumor
Humans
metastasis
Biotinylation
Epithelial–mesenchymal transition
Fetuins
Neoplasm Staging
biology
medicine.diagnostic_test
Staining and Labeling
Liver Neoplasms
biomarkers
Cell Biology
hepatocellular carcinoma
Middle Aged
medicine.disease
Flow Cytometry
Neoplastic Cells
Circulating
Prognosis
Neoplasm Proteins
Hepatocellular carcinoma
biology.protein
Disease Progression
Asialoglycoprotein receptor
Female
Original Article
Zdroj: Cell Death & Disease
ISSN: 2041-4889
Popis: The presence of circulating tumor cells (CTCs) in peripheral blood is associated with metastasis and prognosis in hepatocellular carcinoma (HCC) patients. The epithelial–mesenchymal transition (EMT) has a pivotal role in tumor invasion and dissemination. To identify more sensitive biomarkers for evaluating metastasis and prognosis, we investigated the expression of EMT markers, including vimentin, twist, ZEB1, ZEB2, snail, slug and E-cadherin in CTCs, primary HCC tumors and adjacent non-tumoral liver tissues. After isolating viable CTCs from the peripheral blood of HCC patients using asialoglycoprotein receptors (ASGPRs), the CTCs were identified with immunofluorescence staining. CTCs were detected in the peripheral blood obtained from 46 of 60 (76.7%) HCC patients. Triple-immunofluorescence staining showed that twist and vimentin expression could be detected in CTCs obtained from 39 (84.8%) and 37 (80.4%) of the 46 patients, respectively. The expression of both twist and vimentin in CTCs was significantly correlated with portal vein tumor thrombus. Coexpression of twist and vimentin in CTCs could be detected in 32 (69.6%) of the 46 patients and was highly correlated with portal vein tumor thrombus, TNM classification and tumor size. Quantitative fluorescence western blot analysis revealed that the expression levels of E-cadherin, vimentin and twist in HCC tumors were significantly associated with the positivity of isolated CTCs (P=0.013, P=0.012, P=0.009, respectively). However, there was no significant difference in ZEB1, ZEB2, snail and slug expression levels in CTCs, primary HCC tumors and adjacent non-tumoral liver tissues across samples with regard to the clinicopathological parameters. Our results demonstrate that the EMT has a role in promoting the blood-borne dissemination of primary HCC cells, and the twist and vimentin expression levels in CTCs could serve as promising biomarkers for evaluating metastasis and prognosis in HCC patients.
Databáze: OpenAIRE
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