J Cancer 2020; 11(11):3400-3406. doi:10.7150/jca.41090 This issue

Research Paper

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

Jie Zhang1*, Ya-Peng Qi1*, Ning Ma2, Fei Lu1, Weng-Feng Gong1, Bin Chen1, Liang Ma1, Jian-Hong Zhong1✉, Bang-De Xiang1✉, Le-Qun Li1

1. Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Guangxi, China
2. Graduate School of Health Science, Suzuka University of Medical Science, Suzuka, Japan
*Jie Zhang and Ya-Peng Qi contributed equally to this work.

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.
Zhang J, Qi YP, Ma N, Lu F, Gong WF, Chen B, Ma L, Zhong JH, Xiang BD, Li LQ. Overexpression of Epcam and CD133 Correlates with Poor Prognosis in Dual-phenotype Hepatocellular Carcinoma. J Cancer 2020; 11(11):3400-3406. doi:10.7150/jca.41090. Available from https://www.jcancer.org/v11p3400.htm

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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.

Keywords: dual-phenotype hepatocellular carcinoma, prognosis, Cancer stem cells, CD133, EpCAM