title: In silico dissection of cell-type-associated patterns of gene expression in prostate cancer.
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.
authors.affiliation: Veterans Affairs San Diego Healthcare System, and Department of Medicine and John and Rebecca Moores UCSD Cancer Center, University of California at San Diego, La Jolla, USA.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Stuart
authors.forename: William
authors.initials: W
authors.lastname: Wachsman
authors.forename: Charles C
authors.initials: CC
authors.lastname: Berry
authors.forename: Jessica
authors.initials: J
authors.lastname: Wang-Rodriguez
authors.forename: Linda
authors.initials: L
authors.lastname: Wasserman
authors.forename: Igor
authors.initials: I
authors.lastname: Klacansky
authors.forename: Dan
authors.initials: D
authors.lastname: Masys
authors.forename: Karen
authors.initials: K
authors.lastname: Arden
authors.forename: Steven
authors.initials: S
authors.lastname: Goodison
authors.forename: Michael
authors.initials: M
authors.lastname: McClelland
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Wang
authors.forename: Anne
authors.initials: A
authors.lastname: Sawyers
authors.forename: Iveta
authors.initials: I
authors.lastname: Kalcheva
authors.forename: David
authors.initials: D
authors.lastname: Tarin
authors.forename: Dan
authors.initials: D
authors.lastname: Mercola
mesh_terms: D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009693:Nucleic Acid Hybridization; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology