Identification of molecular markers for the oncogenic differentiation of hepatocellular carcinoma.
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.
Division of Gastroenterology and Hepatology, The Research Institute of Clinical Medicine, Department of Internal Medicine, Chonbuk National University Medical School and Hospital, Jeonju 561-712, Korea.
Gyung Ran
GR
Yu
Seong Hun
SH
Kim
Seon Hwa
SH
Park
Xiang Dan
XD
Cui
Dong Yuan
DY
Xu
Hee Chul
HC
Yu
Baik Hwan
BH
Cho
Young Il
YI
Yeom
Sang Soo
SS
Kim
Sang Bae
SB
Kim
In Sun
IS
Chu
Dae Ghon
DG
Kim
D017306:Annexin A2 / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D018832:Molecular Chaperones / Q000235:genetics; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes
C472822:ANXA2 protein, human; D017306:Annexin A2; D014408:Biomarkers, Tumor; D018832:Molecular Chaperones