An apoptotic molecular network identified by microarray: on the TRAIL to new insights in epithelial ovarian cancer.
BACKGROUND
In a previous microarray expression analysis, the authors identified candidate genes that were expressed differentially between ovarian tumors with low malignant potential and invasive serous epithelial ovarian tumors. Among them, the apoptosis-related candidate genes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), caspase 8 (CASP8), FLICE-inhibitory protein (FLIP), and cytochrome C (CYC) were identified.


METHODS
For the current study, the authors conducted immunohistochemical analyses of a tissue array comprised of 235 serous tumors of different grades and stages to evaluate whether there was differential protein expression for these candidates and for the 4 death cell receptors of Trail: Dr4, Dr5, DcR1, and DcR2.


RESULTS
All proteins except DcR1 and DcR2 had significantly differential expression levels between grade 0 tumors (low malignant potential) and grade 2 and 3 tumors. Trail also showed differential expression between grade 0 tumors and grade 1 tumors. When all tumors were compared, the expression levels of Trail, Dr4, Dr5, DcR1, and Flip differed significantly between early-stage and advanced-stage disease. High Dr5 expression was associated with a poor prognosis in patients who had invasive tumors and in the subgroup of patients who had grade 3 tumors. Furthermore, the combinations of 2 proteins (Trail and Dr5, DcR2 and Cyc, Flip and Dr5, Flip and DcR2, DcR1 and Dr5 or Dr4 and Flip) revealed an association with patient prognosis.


CONCLUSIONS
The identification of new proteins in the initial diagnosis and prognosis of patients with epithelial ovarian cancer may lead to a better understanding of the disease, highlighting new potential therapeutic targets, and may be useful in patient management.
Ouellet
Véronique
V
The Research Centre of the University of Montreal Teaching Hospital (CR-CHUM)/Montreal Cancer Institute, Montreal, Quebec, Canada.
Le Page
Cécile
C
Madore
Jason
J
Guyot
Marie-Claude
MC
Barrès
Véronique
V
Lussier
Christian
C
Tonin
Patricia N
PN
Provencher
Diane M
DM
Mes-Masson
Anne-Marie
AM
D017209:Apoptosis / Q000235:genetics*; D005260:Female; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D011379:Prognosis; D016019:Survival Analysis; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000502:physiology*
D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human