Integrative genomic identification of genes on 8p associated with hepatocellular carcinoma progression and patient survival.
Integrative genomic identification of genes on 8p associated with hepatocellular carcinoma progression and patient survival.
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DOI：
10.1053/j.gastro.2011.12.039
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发表时间：
2012-04
期刊：
影响因子：
29.4
通讯作者：
Wang XW
中科院分区：
文献类型：
--
作者：
Roessler S;Long EL;Budhu A;Chen Y;Zhao X;Ji J;Walker R;Jia HL;Ye QH;Qin LX;Tang ZY;He P;Hunter KW;Thorgeirsson SS;Meltzer PS;Wang XW
肝细胞癌是一种侵袭性的恶性肿瘤，其发生发展机制尚不清楚。我们使用一种综合的方法来识别肝癌驱动基因，其定义是其拷贝数与基因表达和癌症进展相关的基因。我们结合了高分辨率、基于阵列的比较基因组杂交(CGH)和转录组分析的数据，这些数据来自76名乙肝病毒感染患者的肝癌样本，以及患者生存时间的数据。候选基因使用体外和体内模型进行了功能验证。对阵列CGH数据的非监督分析与染色体8p的丢失相关，结果较差(存活时间缩短)；体细胞拷贝数改变与所分析基因中27.3%的表达相关。我们在2个独立队列(包括319例混合病因的肝细胞癌)和3个乳腺癌队列(637例)中，将其中10个基因的表达水平与患者的生存时间相关联。在10个基因标记中，预后较差的患者肝细胞癌中8p上的6个基因(DLC1、CCDC25、ELP3、PROSC、SH2D4A和SORBS3)缺失。体外和体内分析表明，PROSC、SH2D4A和SORBS3的产物以及已知的肿瘤抑制基因DLC1都具有抑瘤活性。我们使用一种公正的方法确定了10个与肝细胞癌进展相关的基因。这些可能用于辅助诊断和根据基因表达模式对肿瘤进行分期。
Hepatocellular carcinoma (HCC) is an aggressive malignancy; its mechanisms of development and progression are poorly understood. We used an integrative approach to identify HCC driver genes, defined as genes whose copy numbers associate with gene expression and cancer progression. We combined data from high-resolution, array-based comparative genomic hybridization (CGH) and transcriptome analysis of HCC samples from 76 patients with hepatitis B virus infection with data on patient survival times. Candidate genes were functionally validated using in vitro and in vivo models. Unsupervised analyses of array CGH data associated loss of chromosome 8p with poor outcome (reduced survival time); somatic copy number alterations correlated with expression of 27.3% of genes analyzed. We associated expression levels of 10 of these genes with patient survival times in 2 independent cohorts (comprising 319 cases of HCC with mixed etiology) and 3 breast cancer cohorts (637 cases). Among the 10-gene signature, a cluster of 6 genes on 8p, (DLC1, CCDC25, ELP3, PROSC, SH2D4A, and SORBS3) were deleted in HCCs from patients with poor outcomes. In vitro and in vivo analyses indicated that the products of PROSC, SH2D4A, and SORBS3 have tumor-suppressive activities, along with the known tumor suppressor gene, DLC1. We used an unbiased approach to identify 10 genes associated with HCC progression. These might be used in assisting diagnosis and to stage tumors based on gene expression patterns.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
DOI：
10.1056/nejmoa0901282
发表时间：
2009-10-08
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ji J;Shi J;Budhu A;Yu Z;Forgues M;Roessler S;Ambs S;Chen Y;Meltzer PS;Croce CM;Qin LX;Man K;Lo CM;Lee J;Ng IO;Fan J;Tang ZY;Sun HC;Wang XW
通讯作者：
Wang XW
影响因子：
2.1
作者：
Irizarry, RA;Hobbs, B;Speed, TP
通讯作者：
Speed, TP