Gene expression patterns that characterize advanced stage serous ovarian cancers.
OBJECTIVE
To identify gene expression patterns that characterize advanced stage serous ovarian cancers by using microarray expression analysis.


METHODS
Using genome-wide expression analysis, we compared a series of 31 advanced stage (III or IV) serous ovarian cancers from patients who survived either less than 2 years or more than 7 years with three normal ovarian epithelial samples. Array findings were validated by analysis of expression of the insulin-like growth factor binding protein 2 (IGFBP2) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) genes using quantitative real-time polymerase chain reaction (QRT-PCR).


RESULTS
Hierarchical clustering identified patterns of gene expression that distinguished cancer from normal ovarian epithelium. We also identified gene expression patterns that distinguish cancers on the basis of patient survival. These genes include many that are associated with immune function. Expression of IGFBP2 and TRAIL genes measured by array and QRT-PCR analysis demonstrated correlation coefficients of 0.63 and 0.78, respectively.


CONCLUSIONS
Global expression analysis can identify expression patterns and individual genes that contribute to ovarian cancer development and outcome. Many of the genes that determine ovarian cancer survival are associated with the immune response, suggesting that immune function influences ovarian cancer virulence. With the generation of newer arrays with more transcripts, larger studies are possible to fully characterize genetic signatures that predict survival that may ultimately be used to guide therapeutic decision-making.
Lancaster
Johnathan M
JM
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Dressman
Holly K
HK
Whitaker
Regina S
RS
Havrilesky
Laura
L
Gray
Jonathan
J
Marks
Jeffrey R
JR
Nevins
Joseph R
JR
Berchuck
Andrew
A
D051017:Apoptosis Regulatory Proteins; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000401:mortality; D004848:Epithelium / Q000737:chemistry; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007109:Immunity / Q000235:genetics; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics; D016014:Linear Models; D008562:Membrane Glycoproteins / Q000235:genetics; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality; D010053:Ovary / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011379:Prognosis; D015996:Survival Rate; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D018971:Insulin-Like Growth Factor Binding Protein 2; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha