Basic—Liver, Pancreas, and Biliary TractEpCAM-Positive Hepatocellular Carcinoma Cells Are Tumor-Initiating Cells With Stem/Progenitor Cell Features
Section snippets
Clinical Specimens
HCC samples were obtained with informed consent from patients who underwent radical resection at the Liver Cancer Institute of Fudan University, Eastern Hepatobiliary Surgery Institute, and the Liver Disease Center of Kanazawa University Hospital, and the study was approved by the institutional review boards of the respective institutes. The microarray data from clinical specimens are available publicly (GEO accession number, GSE5975).27 Array data from a total of 156 HCC cases (155 hepatitis B
A Poor Prognostic HCC Subtype With Molecular Features of HpSC
We re-evaluated the gene expression profiles that were uniquely associated with 2 recently identified prognostic subtypes of HCC (ie, HpSC-HCC and MH-HCC), using a publicly available microarray dataset of 156 HCC cases (GEO accession number: GSE5975). Sixty cases were defined as HpSC-HCC with a poor prognosis and 96 cases were defined as MH-HCC with a good prognosis, based on EpCAM and AFP status.27 A class-comparison analysis with univariate t tests and a global permutation test (1000×)
Discussion
The cellular origin of HCC is currently in debate. In this study, we found that EpCAM can serve as a marker to enrich HCC cells with tumor-initiating ability and with some stem/progenitor cell traits. EpCAM is expressed in many human cancers with an epithelial origin.39 During embryogenesis, EpCAM is expressed in fertilized oocytes, embryonic stem cells, and embryoid bodies, suggesting its role in early stage embryogenesis.40 Furthermore, a recent article indicated that EpCAM is expressed in
Acknowledgments
Microarray data are available publicly at http://www.ncbi.nlm.nih.gov/geo/ (accession number: GSE5975).
The authors thank Drs Curtis Harris and Sharon Pine for critical readings of the manuscript; Ms Barbara Taylor and Dr Susan Garfield for technical assistance; Drs Ali Brivanlou (Rockefeller University), Steve Strom (University of Pittsburgh), and Bert Vogelstein (Johns Hopkins University) for generously providing their research materials.
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Conflicts of interest The authors disclose no conflicts.
Funding The authors disclose the following: This work was supported in part by the Intramural Research Program of the Center for Cancer Research, the US National Cancer Institute. Dr Yang, Dr HY Wang, Dr Jia, Dr Ye, Dr Qin, and Dr Tang were supported by research grants from the China National Natural Science Foundation for Distinguished Young Scholars (30325041) and the China National “863” R&D High-Tech Key Project (2002BA711A02-4). Dr Reid was supported by a sponsored research grant from Vesta Therapeutics (Research Triangle Park, NC), National Institutes of Health grants (RO1 AA014243 and RO1 IP30-DK065933), and a US Department of Energy grant (DE-FG02-02ER-63477). Sponsors had no role in the study design, data collection, analysis, and interpretation. Dr Yamashita, Dr Ji, Dr Budhu, Dr Forgues, Dr Yang, Dr Wang, Dr Jia, Dr Ye, Dr Wauthier, Dr Minato, Dr Honda, Dr Kaneko, and Dr Wang disclose no conflicts.