In silico dissection of cell-type-associated patterns of gene expression in prostate cancer.
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.
Stuart
Robert O
RO
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.
Wachsman
William
W
Berry
Charles C
CC
Wang-Rodriguez
Jessica
J
Wasserman
Linda
L
Klacansky
Igor
I
Masys
Dan
D
Arden
Karen
K
Goodison
Steven
S
McClelland
Michael
M
Wang
Yipeng
Y
Sawyers
Anne
A
Kalcheva
Iveta
I
Tarin
David
D
Mercola
Dan
D
D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009693:Nucleic Acid Hybridization; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology