Identification of a mRNA Protease Profile Associated with Early Relapse in Serous Ovarian Cancer
D Trudel, I Bairati, CM Overall, R Kappelhoff, M Plante, B Tetu. Centre Hospitalier Universitaire de Québec, Québec, Canada; University of British Columbia, Vancouver, Canada
Background: Mostly diagnosed at an advanced stage (FIGO III or more), patients with OC usually respond well to chemotherapy. However, at 18 months, about 60% of women with complete response to treatment relapse. Expression of proteases (such as kallikreins) have been associated with OC prognosis. The proteins are mostly secreted by stromal cells but some are mainly secreted by tumour cells. Our objective is to test the hypothesis that a specific mRNA protease profile allows the identification of women with serous OC who experience early relapse after a complete response to standard treatment.
Design: Ten stage III tumours from cytoreductive surgical specimen were selected from our tissue bank. After treatment with platinum-paclitaxel, these women were in complete response as defined by serum CA-125 levels and they were divided in two groups of 5 women according to their time to relapse as early relapse (ER) or late relapse (LR). Snap-frozen tissue was micro-dissected to isolate stromal cells from tumour cells. mRNA was extracted from stromal cells and from tumour cells. A microarray dedicated to proteases study (CLIP-CHIP) was used to determine gene expression in both cell types. For each gene, expression in ER group was compared to expression in LR group. P-values were estimated using the empirical bayes method of Smyth within the limma package in Bioconductor and then adjusted following the Benjamini-Hochberg procedure.
Results: mRNA was available from tumors of all women and from stroma of 8 women, 4 with ER and 4 with LR. Mean time to relapse was 356.2 days in the ER group and 1137.4 days in the late relapse (LR) group. In the ER group, among 27 significant genes, WAP four-disulfide core-2 (WDFC2, HE4) was overexpressed 5.1 times (adjusted p= 0.047), ADAM-10 was overexpressed 8.7 times (adjusted p = 0.028) and proteasome beta-1 subunit (PSMB1) was underexpressed 4.1 times (adjusted p = 0.015).
Conclusions: To our knowledge, this is the first study aimed at identifying a set of proteases associated with prognosis in women with OC and complete response after standard treatment. These findings may help to better understand the biology of OC and to develop targeted treatment strategies.
Category: Gynecologic & Obstetrics
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 152, Wednesday Afternoon