Multiple oncogenic pathway signatures show coordinate expression patterns in human prostate tumors.
Multiple oncogenic pathway signatures show coordinate expression patterns in human prostate tumors.
复制标题
多种致癌途径特征显示人类前列腺肿瘤中的坐标表达模式。
DOI：
10.1371/journal.pone.0001816
复制
发表时间：
2008-03-19
期刊：
影响因子：
3.7
通讯作者：
Creighton, Chad J.
中科院分区：
文献类型：
--
作者：
Creighton, Chad J.
与癌基因Myc、c-Src、β-连环蛋白、E2 F3、H-Ras、HER 2、EGFR、MEK、Raf、MAPK、Akt和细胞周期蛋白D1以及细胞周期和雄激素信号传导的激活相关的基因转录模式已在先前的研究中使用实验模型产生。目前尚不清楚这些“致癌标签”中的基因是否会在人类前列腺肿瘤中显示出协调表达模式，特别是因为大多数标签来自前列腺以外的细胞类型。使用Q1-Q2和单侧Fisher精确富集分析方法，在人前列腺肿瘤的四个不同基因表达谱数据集中检查上述致癌途径特征（总共代表10250名患者）。在人类肿瘤中，由Myc、c-Src、HER 2、Akt或雄激素实验上调的基因的显著部分（约5%）与对应于通路特征的致癌基因或生物标志物共表达。然而，实验下调的基因在人类肿瘤中没有显示出预期的抗富集模式。这些实验衍生的致癌标签中的基因的重要子集与人类前列腺癌的研究相关。分子生物学家和临床研究人员都可以将注意力集中在相对较少的基因上，这些基因在实验系统和人类疾病系统中都具有协调模式。
Gene transcription patterns associated with activation of oncogenes Myc, c-Src, beta-catenin, E2F3, H-Ras, HER2, EGFR, MEK, Raf, MAPK, Akt, and cyclin D1, as well as of the cell cycle and of androgen signaling have been generated in previous studies using experimental models. It was not clear whether genes in these “oncogenic signatures” would show coordinate expression patterns in human prostate tumors, particularly as most of the signatures were derived from cell types other than prostate. The above oncogenic pathway signatures were examined in four different gene expression profile datasets of human prostate tumors (representing ∼250 patients in all), using both Q1-Q2 and one-sided Fisher's exact enrichment analysis methods. A significant fraction (∼5%) of genes up-regulated experimentally by Myc, c-Src, HER2, Akt, or androgen were co-expressed in human tumors with the oncogene or biomarker corresponding to the pathway signature. Genes down-regulated experimentally, however, did not show anticipated patterns of anti-enrichment in the human tumors. Significant subsets of the genes in these experimentally-derived oncogenic signatures are relevant to the study of human prostate cancer. Both molecular biologists and clinical researchers could focus attention on the relatively small number of genes identified here as having coordinate patterns that arise from both the experimental system and the human disease system.
登录
查看更多内容
影响因子：
82.9
作者：
Chen, CD;Welsbie, DS;Sawyers, CL
通讯作者：
Sawyers, CL
影响因子：
11.2
作者：
Deeb, Kristin K.;Michalowska, Aleksandra M.;Green, Jeffrey E.
通讯作者：
Green, Jeffrey E.
影响因子：
6
作者：
Paronetto, MP;Farini, D;Sette, C
通讯作者：
Sette, C
影响因子：
11.2
作者：
Creighton, CJ;Hilger, AM;El-Ashry, D
通讯作者：
El-Ashry, D
影响因子：
64.5
作者：
Lamb, J;Ramaswamy, S;Ewen, ME
通讯作者：
Ewen, ME