High expression of tumor necrosis factor-related apoptosis-inducing ligand is associated with favorable ovarian cancer survival.
OBJECTIVE
The molecular determinants of survival in ovarian cancer are poorly understood. Using expression microarrays, we recently found that high expression of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene is associated with prolonged survival in advanced ovarian cancer. TRAIL has also been shown to synergize with chemotherapeutic agents to induce apoptosis in ovarian cancer cell lines. We therefore sought to confirm the association between TRAIL expression and survival in a larger group of women with ovarian cancer.


METHODS
TRAIL expression was measured using quantitative real-time PCR in 120 epithelial ovarian cancers (11 stage I/II, 109 stage III/IV) and 8 normal ovarian surface epithelial samples.


RESULTS
Ovarian cancers demonstrated 10-fold higher mean TRAIL expression than normal ovarian epithelial samples (P < 0.001). Among ovarian cancers, high TRAIL expression was associated with prolonged survival and was 2.2-fold higher in cancers from patients who lived more than 5 years compared with patients who died within 1 year (P = 0.03).


CONCLUSIONS
TRAIL expression is higher in ovarian cancers relative to normal ovarian epithelium. High TRAIL expression is associated with favorable ovarian cancer survival, which may be attributable to increased chemosensitivity of cancers that express the most TRAIL. The use of TRAIL to enhance sensitivity of ovarian cancers to therapy represents an appealing molecular therapeutic strategy worthy of further investigation.
Lancaster
Johnathan M
JM
Department of Obstetrics and Gynecology/Division of Gynecologic Oncology, Duke University Medical Center, Durham, North Carolina 27720, USA.
Sayer
Robyn
R
Blanchette
Carrie
C
Calingaert
Brian
B
Whitaker
Regina
R
Schildkraut
Joellen
J
Marks
Jeffrey
J
Berchuck
Andrew
A
D051017:Apoptosis Regulatory Proteins; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D053221:TNF-Related Apoptosis-Inducing Ligand; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha