Expression of contactin associated protein-like 2 in a subset of hepatic progenitor cell compartment identified by gene expression profiling in hepatitis B virus-positive cirrhosis.
BACKGROUND
Hepatic progenitor cells (HPC), a cell compartment capable of differentiating into hepatocytic and biliary lineages, may give rise to the formation of intermediate hepatobiliary cells (IHBC) or ductular reactions (DR).


OBJECTIVE
The aim of this study was to analyse the gene expression profiles of DR in cirrhosis and further investigate novel proteins expressed by HPC and their intermediate progeny.


METHODS
DR in hepatitis B virus (HBV)-positive cirrhotic liver tissues adjacent to hepatocellular carcinoma and interlobular bile ducts (ILBDs) in normal liver tissues were isolated by laser capture microdissection and then subjected to microarray analysis. Differential gene expression patterns were verified by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry on serial sections. HPC and their intermediate progeny were recognized by immunostaining with hepatocytic and biliary markers [HepPar1, cytokeratin (CK)7, CK19, neural cell adhesion molecule (NCAM), epithelial cell adhesion molecule (EpCAM)].


RESULTS
A total of 88 genes showed upregulation in DR compared with ILBDs. Gene ontology analyses revealed that these upregulated genes were mostly associated with cell adhesion, immune response and the metabolic process. Contactin associated protein-like 2 (CNTNAP2) was first confirmed to be a novel protein expressed in a subpopulation of DR that was positive for CK7, NCAM or EpCAM. In addition, immunoreactivity for CNTNAP2 was also noted in a subset of isolated CK7-positive HPC as well as some ductular IHBC positive for CK19 and HepPar1 in DR.


CONCLUSIONS
CNTNAP2 is specifically associated with the emergence of ductular populations and may be identified as a novel protein for defining a subset of HPC and their intermediate progeny in cirrhosis.
Wang
Huafeng
H
Department of Pathology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Gao
Yabo
Y
Jin
Xiaolong
X
Xiao
Jiacheng
J
D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology / Q000821:virology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics* / Q000378:metabolism; D019070:Cell Lineage; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006498:Hepatectomy; D019694:Hepatitis B, Chronic / Q000150:complications / Q000235:genetics* / Q000473:pathology; D022781:Hepatocytes / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation
D015415:Biomarkers; C491323:CNTNAP1 protein, human; D015816:Cell Adhesion Molecules, Neuronal