Integrative genomic signatures of hepatocellular carcinoma derived from nonalcoholic Fatty liver disease.
Integrative genomic signatures of hepatocellular carcinoma derived from nonalcoholic Fatty liver disease.
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DOI：
10.1371/journal.pone.0124544
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Martínez-Chantar ML
中科院分区：
文献类型：
--
作者：
Frades I;Andreasson E;Mato JM;Alexandersson E;Matthiesen R;Martínez-Chantar ML
非酒精性脂肪性肝病(NAFLD)是肝细胞癌(肝细胞癌)的危险因素，但人们对NAFLD向肝细胞癌的转变知之甚少。在人类和转基因小鼠的NAFLD和肝癌微阵列数据中应用特征选择算法来生成NAFLD进展和肝癌差异生存的信号。这些信号被用来研究NAFLD来源的肝癌的发病机制，并探索哪些癌症亚型可以用小鼠模型进行研究。我们的发现表明：(I)HNF4是一种共同的潜在转录因子，介导NAFLD进展基因的转录(Ii)来自NAFLD共同集群的小鼠肝癌具有不同预后和混合病因的侵袭性较低的人肝癌亚型(Iii)肝细胞癌生存特征能够正确地对95%的样本进行分类，并给予FGF20和Tgfb1i1作为最稳健的预测基因(Iv)在独立的人类肝细胞癌数据集中组成特征基因的表达值显示不同的肝细胞癌亚型通过LOGRANK检验显示生存时间的差异。综上所述，我们提出了NAFLD衍生的肝细胞癌分子发病机制的基因和途径水平的标记信号。
Nonalcoholic fatty liver disease (NAFLD) is a risk factor for Hepatocellular carcinoma (HCC), but he transition from NAFLD to HCC is poorly understood. Feature selection algorithms in human and genetically modified mice NAFLD and HCC microarray data were applied to generate signatures of NAFLD progression and HCC differential survival. These signatures were used to study the pathogenesis of NAFLD derived HCC and explore which subtypes of cancers that can be investigated using mouse models. Our findings show that: (I) HNF4 is a common potential transcription factor mediating the transcription of NAFLD progression genes (II) mice HCC derived from NAFLD co-cluster with a less aggressive human HCC subtype of differential prognosis and mixed etiology (III) the HCC survival signature is able to correctly classify 95% of the samples and gives Fgf20 and Tgfb1i1 as the most robust genes for prediction (IV) the expression values of genes composing the signature in an independent human HCC dataset revealed different HCC subtypes showing differences in survival time by a Logrank test. In summary, we present marker signatures for NAFLD derived HCC molecular pathogenesis both at the gene and pathway level.
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影响因子：
13.5
作者：
Jover, R;Bort, R;Castell, JV
通讯作者：
Castell, JV
影响因子：
64.8
作者：
Bild, AH;Yao, G;Nevins, JR
通讯作者：
Nevins, JR
影响因子：
2.1
作者：
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通讯作者：
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DOI：
10.1073/pnas.0802690105
发表时间：
2008-05-06
影响因子：
11.1
作者：
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通讯作者：
Weisinger, Richard S.
影响因子：
3.9
作者：
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通讯作者：
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