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ABSTRACT: Purpose
This study assesses the ability of multidrug resistance (MDR)-associated gene expression patterns to predict survival in patients with newly diagnosed carcinoma of the ovary. The scope of this research differs substantially from that of previous reports, as a very large set of genes was evaluated whose expression has been shown to affect response to chemotherapy.Experimental design
We applied a customized TaqMan low density array, a highly sensitive and specific assay, to study the expression profiles of 380 MDR-linked genes in 80 tumor specimens collected at initial surgery to debulk primary serous carcinoma. The RNA expression profiles of these drug resistance genes were correlated with clinical outcomes.Results
Leave-one-out cross-validation was used to estimate the ability of MDR gene expression to predict survival. Although gene expression alone does not predict overall survival (OS; P = 0.06), four covariates (age, stage, CA125 level, and surgical debulking) do (P = 0.03). When gene expression was added to the covariates, we found an 11-gene signature that provides a major improvement in OS prediction (log-rank statistic P < 0.003). The predictive power of this 11-gene signature was confirmed by dividing high- and low-risk patient groups, as defined by their clinical covariates, into four specific risk groups on the basis of expression levels.Conclusion
This study reveals an 11-gene signature that allows a more precise prognosis for patients with serous cancer of the ovary treated with carboplatin- and paclitaxel-based therapy. These 11 new targets offer opportunities for new therapies to improve clinical outcome in ovarian cancer.
SUBMITTER: Gillet JP
PROVIDER: S-EPMC3376649 | biostudies-literature | 2012 Jun
REPOSITORIES: biostudies-literature
Gillet Jean-Pierre JP Calcagno Anna Maria AM Varma Sudhir S Davidson Ben B Bunkholt Elstrand Mari M Ganapathi Ram R Kamat Aparna A AA Sood Anil K AK Ambudkar Suresh V SV Seiden Michael V MV Rueda Bo R BR Gottesman Michael M MM
Clinical cancer research : an official journal of the American Association for Cancer Research 20120405 11
<h4>Purpose</h4>This study assesses the ability of multidrug resistance (MDR)-associated gene expression patterns to predict survival in patients with newly diagnosed carcinoma of the ovary. The scope of this research differs substantially from that of previous reports, as a very large set of genes was evaluated whose expression has been shown to affect response to chemotherapy.<h4>Experimental design</h4>We applied a customized TaqMan low density array, a highly sensitive and specific assay, to ...[more]