Lee Ju-Seog, Heo Jeonghoon, Libbrecht Louis, Chu In-Sun, Kaposi-Novak Pal, Calvisi Diego F, Mikaelyan Arsen, Roberts Lewis R, Demetris Anthony J, Sun Zongtang, Nevens Frederik, Roskams Tania, Thorgeirsson Snorri S
Lab of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 4146, Bethesda, Maryland 20892, USA.
Nat Med. 2006 Apr;12(4):410-6. doi: 10.1038/nm1377. Epub 2006 Mar 12.
The variability in the prognosis of individuals with hepatocellular carcinoma (HCC) suggests that HCC may comprise several distinct biological phenotypes. These phenotypes may result from activation of different oncogenic pathways during tumorigenesis and/or from a different cell of origin. Here we address whether the transcriptional characteristics of HCC can provide insight into the cellular origin of the tumor. We integrated gene expression data from rat fetal hepatoblasts and adult hepatocytes with HCC from human and mouse models. Individuals with HCC who shared a gene expression pattern with fetal hepatoblasts had a poor prognosis. The gene expression program that distinguished this subtype from other types of HCC included markers of hepatic oval cells, suggesting that HCC of this subtype may arise from hepatic progenitor cells. Analyses of gene networks showed that activation of AP-1 transcription factors in this newly identified HCC subtype might have key roles in tumor development.
肝细胞癌（HCC）患者预后的变异性表明，HCC可能包含几种不同的生物学表型。这些表型可能源于肿瘤发生过程中不同致癌途径的激活和/或不同的细胞起源。在这里，我们探讨HCC的转录特征是否能为肿瘤的细胞起源提供见解。我们将大鼠胎儿肝母细胞和成年肝细胞的基因表达数据与人类和小鼠模型的HCC数据进行了整合。与胎儿肝母细胞具有相同基因表达模式的HCC患者预后较差。将该亚型与其他类型HCC区分开来的基因表达程序包括肝卵圆细胞标志物，这表明该亚型HCC可能起源于肝祖细胞。基因网络分析表明，在这个新发现的HCC亚型中，AP-1转录因子的激活可能在肿瘤发展中起关键作用。
