Creighton Chad J
Division of Biostatistics, Department of Medicine, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, United States of America.
PLoS One. 2008 Mar 19;3(3):e1816. doi: 10.1371/journal.pone.0001816.
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 approximately 250 patients in all), using both Q1-Q2 and one-sided Fisher's exact enrichment analysis methods. A significant fraction (approximately 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.
在先前的研究中，已利用实验模型生成了与癌基因Myc、c-Src、β-连环蛋白、E2F3、H-Ras、HER2、EGFR、MEK、Raf、MAPK、Akt和细胞周期蛋白D1的激活相关的基因转录模式，以及细胞周期和雄激素信号传导的基因转录模式。尚不清楚这些“致癌特征”中的基因在人类前列腺肿瘤中是否会表现出协同表达模式，尤其是因为大多数特征源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，在人类前列腺肿瘤的四个不同基因表达谱数据集中（总共代表约250名患者）检查了上述致癌途径特征。在实验中由Myc、c-Src、HER2、Akt或雄激素上调的基因中有很大一部分（约5%）在人类肿瘤中与对应途径特征的癌基因或生物标志物共表达。然而，在实验中下调的基因在人类肿瘤中并未显示出预期的反富集模式。
这些实验衍生的致癌特征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关注这里确定的相对少数具有协同模式的基因，这些模式源自实验系统和人类疾病系统。
