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.
Yu
Gyung Ran
GR
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.
Kim
Seong Hun
SH
Park
Seon Hwa
SH
Cui
Xiang Dan
XD
Xu
Dong Yuan
DY
Yu
Hee Chul
HC
Cho
Baik Hwan
BH
Yeom
Young Il
YI
Kim
Sang Soo
SS
Kim
Sang Bae
SB
Chu
In Sun
IS
Kim
Dae Ghon
DG
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