Exp Mol Med.  2007 Oct;39(5):641-652.

Identification of molecular markers for the oncogenic differentiation of hepatocellular carcinoma

• Yu GR
• Kim SH
• Park SH
• Cui XD
• Xu DY
• Yu HC
• Cho BH
• Yeom YI
• Kim SS
• Kim SB
• Chu IS
• Kim DG

Abstract

The aim of this study was to identify molecular markers associated with oncogenic differentiation in hepatocellular carcinoma (HCC). Using an unsupervised clustering method with a cDNA microarray, HCC (T) gene expression profiles and corresponding non-tumor tissues (NT) from 40 patients were analyzed. Of total 217 genes, 72 were expressed preferentially in HCC tissues. Among 186 differentially regulated genes, there were molecular chaperone and tumor suppressor gene clusters in the Edmondson grades I and II (GI/II) subclass compared with the liver cirrhosis (LC) subclass. The Edmondson grades III and IV (GIII/IV) subclass with a poor survival (P = 0.0133) contained 122 differentially regulated genes with a cluster containing various metastasis- and invasion-related genes compared with the GI/II subclass. Immunohistochemical analysis revealed that ANXA2, one of the 72 genes preferentially expressed in HCC, was over-expressed in the sinusoidal endothelium and in malignant hepatocytes in HCC. The genes identified in the HCC subclasses will be useful molecular markers for the genesis and progression of HCC. In addition, ANXA2 might be a novel marker for tumor angiogenesis in HCC.

Keyword

angiogenesis; carcinoma, hepatocellular; cell differentiation; gene expression profiling; tumor markers, biological

MeSH Terms

Annexin A2/genetics
Carcinoma, Hepatocellular/*genetics/pathology
Gene Expression Profiling
Genes, Tumor Suppressor
Humans
Liver Neoplasms/*genetics/pathology
Molecular Chaperones/genetics
Multigene Family
Oligonucleotide Array Sequence Analysis
Oncogenes
Tumor Markers, Biological/*genetics