Abstract
BackgroundAdvanced-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. Our aim is to identify a progression-free survival (PFS)-related molecular profile for predicting survival of patients with advanced-stage serous ovarian cancer.Methodology/Principal FindingsAdvanced-stage serous ovarian cancer tissues from 110 Japanese patients who underwent primary surgery and platinum/taxane-based chemotherapy were profiled using oligonucleotide microarrays. We selected 88 PFS-related genes by a univariate Cox model (p<0.01) and generated the prognostic index based on 88 PFS-related genes after adjustment of regression coefficients of the respective genes by ridge regression Cox model using 10-fold cross-validation. The prognostic index was independently associated with PFS time compared to other clinical factors in multivariate analysis [hazard ratio (HR), 3.72; 95% confidence interval (CI), 2.66–5.43; p<0.0001]. In an external dataset, multivariate analysis revealed that this prognostic index was significantly correlated with PFS time (HR, 1.54; 95% CI, 1.20–1.98; p = 0.0008). Furthermore, the correlation between the prognostic index and overall survival time was confirmed in the two independent external datasets (log rank test, p = 0.0010 and 0.0008).Conclusions/SignificanceThe prognostic ability of our index based on the 88-gene expression profile in ridge regression Cox hazard model was shown to be independent of other clinical factors in predicting cancer prognosis across two distinct datasets. Further study will be necessary to improve predictive accuracy of the prognostic index toward clinical application for evaluation of the risk of recurrence in patients with advanced-stage serous ovarian cancer.
Highlights
Patients with advanced-stage ovarian cancer generally undergo primary debulking surgery followed by platinum/taxane-based chemotherapy
We focused on progression-free survival (PFS) time in a larger number of patients only with advanced-stage serous ovarian cancer treated with platinum/taxane-based chemotherapy, and tried to identify PFS-related gene expression profile using a new survival analysis method: ridge regression Cox model [18]
This stratified analysis indicated that the prognostic index was associated with PFS time independently of the debulking status. Correlation between This Prognostic Index and Overall Survival. Overall survival is another important endpoint in patients with advance-stage ovarian cancers, and we further examined if the present 88-gene prognostic index could be extended to use for predicting the overall survival of patients
Summary
Patients with advanced-stage ovarian cancer generally undergo primary debulking surgery followed by platinum/taxane-based chemotherapy. Postoperative introduction of taxane drug has improved the 5-year survival rate for advanced-stage ovarian cancer, patients with this cancer have a 5-year survival rate of only 30% [1,2,3] Clinicopathological characteristics, such as debulking status after primary surgery, are clinically considered important indicators of prognosis [4,5]. It has been reported that 34% of patients treated with optimal surgery and platinum-taxane combination chemotherapy for advanced-stage ovarian cancer recur within 12 months [4]. These clinicopathological factors alone are insufficient for predicting prognosis and elucidating the pathological mechanisms of disease progression or recurrence. Our aim is to identify a progression-free survival (PFS)-related molecular profile for predicting survival of patients with advanced-stage serous ovarian cancer
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