Genome-scale profiling of gene expression in hepatocellular carcinoma: Classification, survival prediction, and identification of therapeutic targets
Genome-scale profiling of gene expression in hepatocellular carcinoma: Classification, survival prediction, and identification of therapeutic targets
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DOI：
10.1053/j.gastro.2004.09.015
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发表时间：
2004-11-01
期刊：
影响因子：
29.4
通讯作者：
Thorgeirsson, SS
中科院分区：
文献类型：
--
作者：
Lee, JS;Thorgeirsson, SS
人类肝细胞癌（HCC）的异质性阻碍了治疗和预后预测。分析人HCC的基因表达谱以确定肿瘤的分子特征并测试表达谱的预后价值。通过应用全局基因表达分析，包括非监督和监督方法，发现了2种不同的HCC亚类，它们在基础生物学和临床结果方面高度同质。低存活亚类的肿瘤具有强的细胞增殖和抗凋亡基因表达特征。此外，低生存率亚类显示参与泛素化和SUMO化的基因的较高表达，表明这些过程在加速HCC进展中的病因参与。通过使用考克斯比例风险生存分析来鉴定与生存最强相关的基因。这种方法确定了有限数量的基因，准确预测生存期的长度，并为HCC的发病机制提供了新的分子见解。未来的研究将评估全球基因表达研究中发现的潜在诊断标记物和治疗靶点。此外，基因表达模式的跨物种相似性也将允许从人类基因表达谱研究中获得的一长串基因的优先顺序，并集中于在两个物种中肿瘤发生期间表达改变的基因。
The heterogeneous nature of human hepatocellular carcinoma (HCC) has hampered both treatment and prognostic predictions. Gene expression profiles of human HCC were analyzed to define the molecular characteristics of the tumors and to test the prognostic value of the expression profiles. By applying global gene expression analyses, including unsupervised and supervised methods, 2 distinctive subclasses of HCC that were highly homogeneous for both the underlying biology and the clinical outcome were discovered. Tumors from the low survival subclass had strong cell proliferation and antiapoptosis gene expression signatures. In addition, the low survival subclass displayed higher expression of genes involved in ubiquitination and sumoylation, suggesting an etiologic involvement of these processes in accelerating the progression of HCC. Genes most strongly associated with survival were identified by using the Cox proportional hazards survival analysis. This approach identified a limited number of genes that accurately predicted the length of survival and provided new molecular insights into the pathogenesis of HCC. Future studies will evaluate potential diagnostic markers and therapeutic targets identified during the global gene expression studies. Furthermore, cross-species similarity of gene expression patterns will also allow prioritization of a long list of genes obtained from human gene expression profiling studies and focus on genes whose expression is altered during tumorigenesis in both species.