Yu Gyung Ran, Kim Seong Hun, Park Seon Hwa, Cui Xiang Dan, Xu Dong Yuan, Yu Hee Chul, Cho Baik Hwan, Yeom Young Il, Kim Sang Soo, Kim Sang Bae, Chu In Sun, Kim Dae Ghon
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.
Exp Mol Med. 2007 Oct 31;39(5):641-52. doi: 10.1038/emm.2007.70.
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.
本研究的目的是鉴定与肝细胞癌（HCC）致癌分化相关的分子标志物。采用cDNA微阵列无监督聚类方法，分析了40例患者的HCC（T）基因表达谱及相应的非肿瘤组织（NT）。在总共217个基因中，72个在HCC组织中优先表达。在186个差异调节基因中，与肝硬化（LC）亚类相比，Edmondson I级和II级（GI/II）亚类中有分子伴侣和肿瘤抑制基因簇。生存较差的Edmondson III级和IV级（GIII/IV）亚类（P=0.0133）与GI/II亚类相比包含122个差异调节基因，其中一个簇包含各种与转移和侵袭相关的基因。免疫组织化学分析显示，72个在HCC中优先表达的基因之一ANXA2，在HCC的窦状内皮和恶性肝细胞中过度表达。在HCC亚类中鉴定出的基因将是HCC发生和进展的有用分子标志物。此外，ANXA2可能是HCC肿瘤血管生成的新标志物。
