Integrative genomics: liver regeneration and hepatocellular carcinoma.
Integrative genomics: liver regeneration and hepatocellular carcinoma.
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DOI：
10.1002/jcb.24104
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发表时间：
2012-07
影响因子：
4
通讯作者：
Barton, Michelle Craig
中科院分区：
文献类型：
--
作者：
Coban, Zeynep;Barton, Michelle Craig
与正常肝组织相比，人类肝细胞癌 (HCC) 中基因表达变化的许多全基因组图谱已被报道。这些数据的层次聚类揭示了不同的模式，强调了人类疾病和小鼠 HCC 模型之间的保守性，并提出了 HCC 异质疾病亚型的具体分类。受到部分肝切除再生挑战的小鼠肝脏基因表达的整体分析揭示了因急性损伤、炎症和重新进入细胞周期而发生的基因表达变化。当我们整合 HCC 小鼠模型中基因表达变化的数据集以及在肝再生特定时间改变的基因表达变化的数据集时，我们看到特定生物途径内基因表达的共享、保守的改变，两者均上调，例如细胞周期、细胞死亡和细胞发育，或下调，例如维生素和矿物质代谢、脂质代谢和分子运输。肝再生和肝癌共有的其他分子机制尚未被发现，可能对肿瘤的发展和复发具有重要意义。这些比较可能提供一种方法来判断肝切除术在 HCC 治疗中如何给该疾病的护理带来挑战。此外，揭示肝再生和 HCC 中共有的肝脏炎症反应、肥大、增殖和结构重塑中保守的途径，以及 HCC 中肿瘤发生和进展的特异性途径，可能会揭示 HCC 中新的生物标志物或潜在的治疗靶点。
Numerous genome wide profiles of gene expression changes in human hepatocellular carcinoma (HCC), compared to normal liver tissue, have been reported. Hierarchical clustering of these data reveal distinct patterns, which underscore conservation between human disease and mouse models of HCC, as well as suggest specific classification of subtypes within the heterogeneous disease of HCC. Global profiling of gene expression in mouse liver, challenged by partial hepatectomy to regenerate, reveals alterations in gene expression that occur in response to acute injury, inflammation and re-entry into cell cycle. When we integrated datasets of gene expression changes in mouse models of HCC and those that are altered at specific times of liver regeneration, we saw shared, conserved alterations in gene expression within specific biological pathways, both up-regulated, e.g. cell cycle, cell death and cellular development, or down-regulated, e.g. vitamin and mineral metabolism, lipid metabolism and molecular transport. Additional molecular mechanisms shared by liver regeneration and HCC, as yet undiscovered, may have important implications in tumor development and recurrence. These comparisons may offer a way to judge how liver resection, in the treatment of HCC, introduces challenges to care of the disease. Further, uncovering the pathways conserved in inflammatory response, hypertrophy, proliferation and architectural remodeling of the liver, which are shared in liver regeneration and HCC, versus those specific to tumor development and progression in HCC, may reveal new biomarkers or potential therapeutic targets in HCC.
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影响因子：
64.5
作者：
Zender, Lars;Spector, Mona S.;Lowe, Scott W.
通讯作者：
Lowe, Scott W.
影响因子：
13.5
作者：
Fausto, N;Campbell, JS;Riehle, KJ
通讯作者：
Riehle, KJ
影响因子：
13.5
作者：
Nam, SW;Park, JY;Lee, JY
通讯作者：
Lee, JY
DOI：
10.1016/s0006-291x(03)00125-6
发表时间：
2003-02-28
影响因子：
3.1
作者：
Conner, EA;Lemmer, ER;Thorgeirsson, SS
通讯作者：
Thorgeirsson, SS
影响因子：
8
作者：
Conner, EA;Lemmer, ER;Thorgeirsson, SS
通讯作者：
Thorgeirsson, SS