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Imaging, Diagnosis, Prognosis |
1 Mayo Clinic Cancer Center, Rochester, Minnesota; 2 University of Texas M.D. Anderson Cancer Center, Houston, Texas; and 3 Millennium Pharmaceuticals, Cambridge, Massachusetts
Requests for reprints: Lynn C. Hartmann, Division of Medical Oncology, Mayo Clinic Cancer Center, 200 First Street Southwest, Rochester, MN 55905. Phone: 507-284-3731; Fax: 507-538-0823; E-mail: hartmann.lynn{at}mayo.edu.
Purpose: Women with advanced epithelial ovarian cancer are routinely treated with platinum-paclitaxel chemotherapy following cytoreductive surgery, yet only 
20% achieve long-term disease-free survival. We hypothesized that differences in gene expression before treatment could distinguish patients with short versus long time to recurrence after administration of platinum-paclitaxel combination chemotherapy.
Experimental Design: To test this hypothesis, gene expression profiling of 79 primary surgically resected tumors from women with advanced-stage, high-grade epithelial ovarian cancer was done using cDNA microarrays containing 30,721 genes. Supervised learning algorithms were applied in an effort to develop a binary classifier that could discriminate women at risk for early (
21 months) versus late (>21 months) relapse after initial chemotherapy.
Results: A 14-gene predictive model was developed using a set of training samples (n = 51) and subsequently tested using an independent set of test samples (n = 28). This model correctly predicted the outcome of 24 of the 28 test samples (86% accuracy) with 95% positive predictive value for early relapse.
Conclusions: Predictive markers for early recurrence can be identified for platinum-paclitaxel combination chemotherapy in primary ovarian carcinoma. The proposed 14-gene model requires further validation.
Key Words: ovarian cancer • DNA microarray • biomarkers • pharmacogenomics
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