Abstract
Abstract Advanced-stage ovarian cancer patients are generally treated with platinum/taxane-based chemotherapy after primary debulking surgery. However, there is a wide range of outcomes for individual patients. Therefore, the clinicopathological factors alone are insufficient for predicting prognosis. To identify a progression-free survival (PFS) related profile for predicting survival, advanced-stage serous ovarian cancer tissues from 110 patients who underwent primary surgery and platinum/taxane-based chemotherapy were profiled using oligonucleotide microarrays. We first selected 88 PFS-related genes by a univariate Cox model (p < 0.01). To avoid overfitting our dataset, we then adjusted regression coefficients of the genes by ridge regression Cox model using 10-fold cross-validation. The prognostic index for each patient based on the 88-gene expression profile with the estimated coefficients was significantly correlated with PFS time as a continuous variable. In multivariate analysis, the prognostic index was independently associated with PFS time compared to other clinical factors [hazard ratio (HR), 4.84; 95% confidence interval (CI), 3.50-6.55; p < 0.001]. This prognostic ability was validated using an external validation dataset (n = 87) and proven by multivariate analysis (HR, 1.25; 95% CI, 1.08-1.45; p = 0.0032). The correlation between the prognostic index and overall survival time was confirmed in the two independent datasets. Furthermore, biological characterization of 88 PFS-related genes mainly highlighted several oncogenic signaling pathways. This PFS-related profile is the first step toward clinical practice for optimizing clinical management for advanced-stage serous ovarian cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2162.
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