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Cited by 717Hepatocellular Carcinoma Treatment and PrognosisLiver physiology and pathologyCancer Cells and Metastasis

EpCAM and α-Fetoprotein Expression Defines Novel Prognostic Subtypes of Hepatocellular Carcinoma

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Yamashita, Taro, Forgues, Marshonna, Wang, Wei, Kim, Jin Woo, Ye, Qinghai, Jia, Huliang, Budhu, Anuradha, Zanetti, Krista A. +4 more·2008·Cancer Research
DOI 10.1158/0008-5472.can-07-6013

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Abstract

The heterogeneous nature of hepatocellular carcinoma (HCC) and the lack of appropriate biomarkers have hampered patient prognosis and treatment stratification. Recently, we have identified that a hepatic stem cell marker, epithelial cell adhesion molecule (EpCAM), may serve as an early biomarker of HCC because its expression is highly elevated in premalignant hepatic tissues and in a subset of HCC. In this study, we aimed to identify novel HCC subtypes that resemble certain stages of liver lineages by searching for EpCAM-coexpressed genes. A unique signature of EpCAM-positive HCCs was identified by cDNA microarray analysis of 40 HCC cases and validated by oligonucleotide microarray analysis of 238 independent HCC cases, which was further confirmed by immunohistochemical analysis of an additional 101 HCC cases. EpCAM-positive HCC displayed a distinct molecular signature with features of hepatic progenitor cells including the presence of known stem/progenitor markers such as cytokeratin 19, c-Kit, EpCAM, and activated Wnt-β-catenin signaling, whereas EpCAM-negative HCC displayed genes with features of mature hepatocytes. Moreover, EpCAM-positive and EpCAM-negative HCC could be further subclassified into four groups with prognostic implication by determining the level of α-fetoprotein (AFP). These four subtypes displayed distinct gene expression patterns with features resembling certain stages of hepatic lineages. Taken together, we proposed an easy classification system defined by EpCAM and AFP to reveal HCC subtypes similar to hepatic cell maturation lineages, which may enable prognostic stratification and assessment of HCC patients with adjuvant therapy and provide new insights into the potential cellular origin of HCC and its activated molecular pathways. [Cancer Res 2008;68(5):1451–61]

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Cited by

Sorted by citations

Authors
Yamashita, T., Forgues, M., Wang, W., Kim, J. W., Ye, Q., Jia, H., Budhu, A., Zanetti, K. A., Chen, Y., Qin, L.-X., Tang, Z.-Y., & Wang, X. W.
Affiliations
  • 1Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis,
  • 4Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
  • Fudan University (CN)
  • National Institutes of Health (US)
  • Center for Cancer Research (US)
ORCID
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2008-03-01
Volume
68
Issue
5
Pages
1451-1461
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
DOI
10.1158/0008-5472.can-07-6013
OpenAlex
W2170845559
Cited by
717
References
2
Citations by year
2026: 7 · 2025: 16 · 2024: 24 · 2023: 26 · 2022: 31 · 2021: 44 · 2020: 49 · 2019: 47 · 2018: 32 · 2017: 44 · 2016: 49 · 2015: 61 · 2014: 46 · 2013: 47 · 2012: 54
FWCI
34.17
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cancer Research (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Science and Technology Commission of Shanghai Municipality
  • National Institutes of Health
  • National Cancer Institute
Topics
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
hepatocellular carcinoma, EpCAM, alpha-fetoprotein, prognostic subtypes, hepatic stem cells, hepatic progenitor cells, gene expression signatures, Wnt/β-catenin signaling, CD117, cytokeratin 19, hepatocyte maturation, biomarkers
MeSH terms
Epithelial Cell Adhesion Molecule, alpha-Fetoproteins, Antigens, Neoplasm, Carcinoma, Hepatocellular, Humans, Immunohistochemistry, Liver Neoplasms, Models, Genetic, Prognosis, Biomarkers, Tumor, Signal Transduction, Cell Adhesion Molecules, Gene Expression Regulation, Neoplastic, Cell Lineage, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Cell Line, Tumor

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