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An apoptotic molecular network identified by microarray: On the TRAIL to new insights in epithelial ovarian cancer
Article first published online: 14 JUN 2007
Copyright © 2007 American Cancer Society
Volume 110, Issue 2, pages 297–308, 15 July 2007
How to Cite
Ouellet, V., Le Page, C., Madore, J., Guyot, M.-C., Barrès, V., Lussier, C., Tonin, P. N., Provencher, D. M. and Mes-Masson, A.-M. (2007), An apoptotic molecular network identified by microarray: On the TRAIL to new insights in epithelial ovarian cancer. Cancer, 110: 297–308. doi: 10.1002/cncr.22812
- Issue published online: 29 JUN 2007
- Article first published online: 14 JUN 2007
- Manuscript Accepted: 6 APR 2007
- Manuscript Revised: 27 MAR 2007
- Manuscript Received: 22 AUG 2006
- Canadian Institutes for Health Research (CIHR). Grant Number: MOP-36056
- Banque de Tissus et de Données du Reseau de Recherche sur le Cancer of the Fonds de la Recherche en Santé du Québec)
- Canadian Tumor Repository Network
- Canderel Fund of the Institut du Cancer de Montreal
- epithelial ovarian cancer;
- low malignant potential/borderline tumors;
- diagnostic and prognostic markers;
- tumor necrosis factor-related apoptosis-inducing ligand (Trail) apoptosis
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.
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.
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.
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. Cancer 2007. © 2007 American Cancer Society.