|
Gene expression patterns
within cell lines are
predictive of chemosensitivity.
BMC Genomics.
2008 Feb 8; 9:74.
Brian Z Ring, 1
Stella Chang,2 L Winston Ring,1
Robert S Seitz,3
and Douglas T Ross1
1Applied Genomics
Inc., Burlingame,
CA,
94010,
USA
2Juvaris
BioTherapeutics, Burlingame, CA, 94010,
USA
3Applied Genomics
Inc., Huntsville,
AL,
35806,
USA
ABSTRACT
BACKGROUND:
The NCI has undertaken
a twenty-year project to characterize compound sensitivity patterns in
a
selected set of sixty tumor derived cell lines. Previous studies have
explored
the relationship between compound sensitivity patterns to gene
expression,
protein expression, and DNA copy number for these same cell lines. A
strong
correlation between the pattern of expression of a biomarker and
sensitivity to
a compound could suggest a clinically interesting biological
relationship
between the two.
RESULTS: We
isolated RNA's and
measured expression of 40000 genes using cDNA microarrays from the
fifty-nine
publicly available cell lines. Analysis of this data set in comparison
with
published gene expression data sets demonstrates a high degree of
reproducibility in expression level measurements even using completely
independent RNA preparations and array technologies. Using the
fifty-nine cell
lines for discovery and an additional seven cell lines for which
extensive
compound sensitivity data were available as a test set, we determined
that
gene-compound pairs with a correlation coefficient above 0.6 had a
false
discovery rate of approximately 5%. Large scale features of the gene
expression
and chemosensitivity data, such as tissue of origin and other
physiological
factors, did not seem to explain the majority of correlations between
gene and
compound patterns.
CONCLUSION: A
comparison of gene
expression and compound sensitivity in panels of cell lines was
demonstrated to
have a relatively high validation and low false discovery rate
supporting the
use of this approach and datasets for identifying candidate biomarkers
and
targeted biologically active compounds.
 |
 |
| |
(website link) |
|
