Cargando…

Overexpression of Epcam and CD133 Correlates with Poor Prognosis in Dual-phenotype Hepatocellular Carcinoma

Background: Dual-phenotype hepatocellular carcinoma (DPHCC) is associated with high rate of post-operative recurrence and low rate of survival, which may reflect the post-operative persistence of cancer stem cells (CSCs). Here we explored the potential correlation between DPHCC and expression of CSC...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Jie, Qi, Ya-Peng, Ma, Ning, Lu, Fei, Gong, Weng-Feng, Chen, Bin, Ma, Liang, Zhong, Jian-Hong, Xiang, Bang-De, Li, Le-Qun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097958/
https://www.ncbi.nlm.nih.gov/pubmed/32231746
http://dx.doi.org/10.7150/jca.41090
_version_ 1783511089982472192
author Zhang, Jie
Qi, Ya-Peng
Ma, Ning
Lu, Fei
Gong, Weng-Feng
Chen, Bin
Ma, Liang
Zhong, Jian-Hong
Xiang, Bang-De
Li, Le-Qun
author_facet Zhang, Jie
Qi, Ya-Peng
Ma, Ning
Lu, Fei
Gong, Weng-Feng
Chen, Bin
Ma, Liang
Zhong, Jian-Hong
Xiang, Bang-De
Li, Le-Qun
author_sort Zhang, Jie
collection PubMed
description Background: Dual-phenotype hepatocellular carcinoma (DPHCC) is associated with high rate of post-operative recurrence and low rate of survival, which may reflect the post-operative persistence of cancer stem cells (CSCs). Here we explored the potential correlation between DPHCC and expression of CSCs markers. Methods: In this retrospective study, we included 19 patients with DPHCC and 61 patients with non-DPHCC treated in 2015 by liver resection. Paraffin-embedded tumor tissue specimens were analyzed using immunohistochemistry as well as immunofluorescence double-staining. Rates of recurrence-free survival and overall survival were compared between the two groups using the Kaplan-Meier method, and expression of the CSC markers CD133, CD90, and EpCAM were compared using real-time quantitative PCR and western blotting. Results: Overall survival rates were significantly lower for patients with DPHCC than patients with non-DPHCC at 1 year (78.9% vs 93.4%), 2 years (52.6% vs 72.1%), and 3 years (42.1% vs 67.2%) (P = 0.019). Multivariate Cox proportional hazard modeling identified CK19 positivity (P = 0.016) and multiple nodules (P = 0.023) as independent predictors of poor recurrence-free survival. Independent predictors of poor overall survival were CK19 positivity (P = 0.032), Barcelona Clinic Liver Cancer stage C (P = 0.025) and carbohydrate antigen 19-9 (CA19-9) >37 ng/ml (P = 0.016). Expression of CD133 and EpCAM mRNA and protein were significantly higher in DPHCC tissue than non-DPHCC tissue, while CD90 expression was similar between the groups. Conclusions: These results suggest that DPHCC is associated with significantly lower overall survival than non-DPHCC, and that the poor prognosis among DPHCC patients may be related to the presence of CSCs expressing CD133 and EpCAM.
format Online
Article
Text
id pubmed-7097958
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Ivyspring International Publisher
record_format MEDLINE/PubMed
spelling pubmed-70979582020-03-30 Overexpression of Epcam and CD133 Correlates with Poor Prognosis in Dual-phenotype Hepatocellular Carcinoma Zhang, Jie Qi, Ya-Peng Ma, Ning Lu, Fei Gong, Weng-Feng Chen, Bin Ma, Liang Zhong, Jian-Hong Xiang, Bang-De Li, Le-Qun J Cancer Research Paper Background: Dual-phenotype hepatocellular carcinoma (DPHCC) is associated with high rate of post-operative recurrence and low rate of survival, which may reflect the post-operative persistence of cancer stem cells (CSCs). Here we explored the potential correlation between DPHCC and expression of CSCs markers. Methods: In this retrospective study, we included 19 patients with DPHCC and 61 patients with non-DPHCC treated in 2015 by liver resection. Paraffin-embedded tumor tissue specimens were analyzed using immunohistochemistry as well as immunofluorescence double-staining. Rates of recurrence-free survival and overall survival were compared between the two groups using the Kaplan-Meier method, and expression of the CSC markers CD133, CD90, and EpCAM were compared using real-time quantitative PCR and western blotting. Results: Overall survival rates were significantly lower for patients with DPHCC than patients with non-DPHCC at 1 year (78.9% vs 93.4%), 2 years (52.6% vs 72.1%), and 3 years (42.1% vs 67.2%) (P = 0.019). Multivariate Cox proportional hazard modeling identified CK19 positivity (P = 0.016) and multiple nodules (P = 0.023) as independent predictors of poor recurrence-free survival. Independent predictors of poor overall survival were CK19 positivity (P = 0.032), Barcelona Clinic Liver Cancer stage C (P = 0.025) and carbohydrate antigen 19-9 (CA19-9) >37 ng/ml (P = 0.016). Expression of CD133 and EpCAM mRNA and protein were significantly higher in DPHCC tissue than non-DPHCC tissue, while CD90 expression was similar between the groups. Conclusions: These results suggest that DPHCC is associated with significantly lower overall survival than non-DPHCC, and that the poor prognosis among DPHCC patients may be related to the presence of CSCs expressing CD133 and EpCAM. Ivyspring International Publisher 2020-03-05 /pmc/articles/PMC7097958/ /pubmed/32231746 http://dx.doi.org/10.7150/jca.41090 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Zhang, Jie
Qi, Ya-Peng
Ma, Ning
Lu, Fei
Gong, Weng-Feng
Chen, Bin
Ma, Liang
Zhong, Jian-Hong
Xiang, Bang-De
Li, Le-Qun
Overexpression of Epcam and CD133 Correlates with Poor Prognosis in Dual-phenotype Hepatocellular Carcinoma
title Overexpression of Epcam and CD133 Correlates with Poor Prognosis in Dual-phenotype Hepatocellular Carcinoma
title_full Overexpression of Epcam and CD133 Correlates with Poor Prognosis in Dual-phenotype Hepatocellular Carcinoma
title_fullStr Overexpression of Epcam and CD133 Correlates with Poor Prognosis in Dual-phenotype Hepatocellular Carcinoma
title_full_unstemmed Overexpression of Epcam and CD133 Correlates with Poor Prognosis in Dual-phenotype Hepatocellular Carcinoma
title_short Overexpression of Epcam and CD133 Correlates with Poor Prognosis in Dual-phenotype Hepatocellular Carcinoma
title_sort overexpression of epcam and cd133 correlates with poor prognosis in dual-phenotype hepatocellular carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097958/
https://www.ncbi.nlm.nih.gov/pubmed/32231746
http://dx.doi.org/10.7150/jca.41090
work_keys_str_mv AT zhangjie overexpressionofepcamandcd133correlateswithpoorprognosisindualphenotypehepatocellularcarcinoma
AT qiyapeng overexpressionofepcamandcd133correlateswithpoorprognosisindualphenotypehepatocellularcarcinoma
AT maning overexpressionofepcamandcd133correlateswithpoorprognosisindualphenotypehepatocellularcarcinoma
AT lufei overexpressionofepcamandcd133correlateswithpoorprognosisindualphenotypehepatocellularcarcinoma
AT gongwengfeng overexpressionofepcamandcd133correlateswithpoorprognosisindualphenotypehepatocellularcarcinoma
AT chenbin overexpressionofepcamandcd133correlateswithpoorprognosisindualphenotypehepatocellularcarcinoma
AT maliang overexpressionofepcamandcd133correlateswithpoorprognosisindualphenotypehepatocellularcarcinoma
AT zhongjianhong overexpressionofepcamandcd133correlateswithpoorprognosisindualphenotypehepatocellularcarcinoma
AT xiangbangde overexpressionofepcamandcd133correlateswithpoorprognosisindualphenotypehepatocellularcarcinoma
AT lilequn overexpressionofepcamandcd133correlateswithpoorprognosisindualphenotypehepatocellularcarcinoma