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  • 标题:In silico dissection of cell-type-associated patterns of gene expression in prostate cancer
  • 本地全文:下载
  • 作者:Robert O. Stuart ; William Wachsman ; Charles C. Berry
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2004
  • 卷号:101
  • 期号:2
  • 页码:615-620
  • DOI:10.1073/pnas.2536479100
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Prostate tumors are complex entities composed of malignant cells mixed and interacting with nonmalignant cells. However, molecular analyses by standard gene expression profiling are limited because spatial information and nontumor cell types are lost in sample preparation. We scored 88 prostate specimens for relative content of tumor, benign hyperplastic epithelium, stroma, and dilated cystic glands. The proportions of these cell types were then linked in silico to gene expression levels determined by microarray analysis, revealing unique cell-specific profiles. Gene expression differences for malignant and nonmalignant epithelial cells (tumor versus benign hyperplastic epithelium) could be identified without being confounded by contributions from stroma that dominate many samples or sacrificing possible paracrine influences. Cell-specific expression of selected genes was validated by immunohistochemistry and quantitative PCR. The results provide patterns of gene expression for these three lineages with relevance to pathogenetic, diagnostic, and therapeutic considerations.
  • 关键词:microarray ; expression profiles ; linear regression ; biomarkers ; paracine
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