multiple oncogenic pathway signatures show coordinate expression patterns in human prostate tumors多个致癌途径签名显示坐标表达模式在人类前列腺肿瘤.pdfVIP

Multiple Oncogenic Pathway Signatures Show Coordinate Expression Patterns in Human Prostate Tumors Chad J. Creighton* Division of Biostatistics, Department of Medicine, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, United States of America Abstract Background: 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. Principal Findings: 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. Conclusions: 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. Citation: Creighton CJ (2008) Multiple Oncogenic