In silico dissection of cell-type-associated patterns of gene expression in prostate cancer

Robert O. Stuart, William Wachsman, Charles C. Berry, Jessica Wang-Rodriguez, Linda Wasserman, Igor Klacansky, Dan Masys, Karen Arden, Steven Goodison, Michael McClelland, Yipeng Wang, Anne Sawyers, Iveta Kalcheva, David Tarin, Dan Mercola

Research output: Contribution to journalArticle

152 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)615-620
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number2
DOIs
StatePublished - Jan 13 2004

Keywords

  • Biomarkers
  • Expression profiles
  • Linear regression
  • Microarray
  • Paracine

ASJC Scopus subject areas

  • General

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    Stuart, R. O., Wachsman, W., Berry, C. C., Wang-Rodriguez, J., Wasserman, L., Klacansky, I., Masys, D., Arden, K., Goodison, S., McClelland, M., Wang, Y., Sawyers, A., Kalcheva, I., Tarin, D., & Mercola, D. (2004). In silico dissection of cell-type-associated patterns of gene expression in prostate cancer. Proceedings of the National Academy of Sciences of the United States of America, 101(2), 615-620. https://doi.org/10.1073/pnas.2536479100