Epithelial cell adhesion molecule is a prognosis marker for intrahepatic cholangiocarcinoma

Abstract Background Recently, we identified a gene signature of intrahepatic cholangiocarcinoma (ICC) stroma and demonstrated its clinical relevance for prognosis. The most upregulated genes included epithelial cell adhesion molecule (EpCAM), a biomarker of cancer stem cells (CSC). We hypothesized t...

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Bibliographic Details
Published in:The Journal of surgical research 2014-11, Vol.192 (1), p.117-123
Main Authors: Sulpice, Laurent, MD, PhD, Rayar, Michel, MD, Turlin, Bruno, MD, PhD, Boucher, Eveline, MD, Bellaud, Pascale, MD, Desille, Mireille, PhD, Meunier, Bernard, MD, Clément, Bruno, PhD, Boudjema, Karim, MD, PhD, Coulouarn, Cédric, PhD
Format: Article
Language:English
Subjects:
AC133 Antigen
Aged
Antigens, CD - genetics
Antigens, CD - metabolism
Antigens, Neoplasm - genetics
Antigens, Neoplasm - metabolism
Bile Duct Neoplasms - genetics
Bile Duct Neoplasms - mortality
Bile Duct Neoplasms - surgery
Bile Ducts, Intrahepatic - surgery
Biomarkers
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Cancer
Cell Adhesion - physiology
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - metabolism
Cholangiocarcinoma - genetics
Cholangiocarcinoma - mortality
Cholangiocarcinoma - surgery
Epithelial Cell Adhesion Molecule
Epithelial Cells - cytology
Female
Follow-Up Studies
Glycoproteins - genetics
Glycoproteins - metabolism
Humans
Hyaluronan Receptors - genetics
Hyaluronan Receptors - metabolism
Intrahepatic cholangiocarcinoma
Life Sciences
Male
Middle Aged
Neoplasm Recurrence, Local - mortality
Peptides - genetics
Peptides - metabolism
Predictive Value of Tests
Prognosis
Proportional Hazards Models
Risk Factors
Surgery
Transcriptome
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Summary:Abstract Background Recently, we identified a gene signature of intrahepatic cholangiocarcinoma (ICC) stroma and demonstrated its clinical relevance for prognosis. The most upregulated genes included epithelial cell adhesion molecule (EpCAM), a biomarker of cancer stem cells (CSC). We hypothesized that CSC biomarkers could predict recurrence of resected ICC. Methods Both functional analysis of the stroma signature previously obtained and immunohistochemistry of 40 resected ICC were performed. The relationships between the expression of CSC markers and clinicopathologic factors including survival were assessed by univariate and multivariable analyzes. Results Gene expression profile of the stroma of ICC highlighted embryonic stem cells signature. Immunohistochemistry on tissue microarray showed at a protein level the increased expression of CSC biomarkers in the stroma of ICC compared with nontumor fibrous liver tissue. The overexpression of EpCAM in the stroma of ICC is an independent risk factor for overall (hazard ratio = 2.6; 95% confidence interval, 1.3–5.1; P  = 0.005) and disease-free survival (hazard ratio = 2.2; 95% confidence interval, 1.2–4.2; P  = 0.012). In addition, the overexpression of EpCAM in nontumor fibrous liver tissue is closely correlated with a worst disease-free survival ( P  = 0.035). Conclusions Our findings provide new arguments for a potential role of CSC on ICC progression supporting the idea that targeting CSC biomarkers might represent a promise personalized treatment.
ISSN:0022-4804
1095-8673
DOI:10.1016/j.jss.2014.05.017