EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma.

By T. Yamashita, M. Forgues, Wei Wang, J. W. Kim, Q. Ye, H. Jia, A. Budhu, Krista A. Zanetti, Yidong Chen, L. Qin and 2 more. Cancer Research, 2008

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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-beta-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 alpha-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.

Subfields: Hepatology, Oncology

View Paper: https://www.semanticscholar.org/paper/5075ef945f55f22092a91d078583c3321881d0de

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Citations in the corpus

Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice (2008, unknown): “95-9544, Zymed). cDNA microarray analysis for 263 HCCs was described previously (Yamashita et al., 2008).”
Focal Gains of Vascular Endothelial Growth Factor A and Molecular Classification of Hepatocellular Carcinoma (2008, background): “Despite all these efforts, only two studies have been able to correlate homogeneous biological tumor patterns with survival outcomes (5, 8), although confirmatory-independent validations are not yet available.”
EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. (2012, background): “None of the biomarkers tested so far fulfil these criteria in HCC, but four just require external validation by independent groups: gene signatures or biomarkers from the tumor (EpCAM signature, G3-proliferation subclass, and miR-26a) [77,135,136] and adjacent tissue (poor-survival signature) [137].”
Hepatocellular carcinoma (HCC): Epidemiology, etiology and molecular classification (2020, background): “Gene signatures associated with EpCAM expression were identified using microarray analysis of 40 primary HCC tissues (Yamashita et al., 2008).”
EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. (2012, background): “None of the biomarkers tested so far fulfil these criteria in HCC, but four just require external validation by independent groups: gene signatures or biomarkers from the tumor (EpCAM signature, G3-proliferation subclass, and miR-26a) [77,135,136] and adjacent tissue (poor-survival signature) [137].”