Abstract
BackgroundOvarian carcinoma is the most important cause of gynecological cancer-related mortality in Western societies. Despite the improved median overall survival in patients receiving chemotherapy regimens such as paclitaxel and carboplatin combination, relapse still occurs in most advanced diseased patients. Increased angiogenesis is associated with rapid recurrence and decreased survival in ovarian cancer. This study was planned to identify an angiogenesis-related gene expression profile with prognostic value in advanced ovarian carcinoma patients.Methodology/Principal FindingsRNAs were collected from formalin-fixed paraffin-embedded samples of 61 patients with III/IV FIGO stage ovarian cancer who underwent surgical cytoreduction and received a carboplatin plus paclitaxel regimen. Expression levels of 82 angiogenesis related genes were measured by quantitative real-time polymerase chain reaction using TaqMan low-density arrays. A 34-gene-profile which was able to predict the overall survival of ovarian carcinoma patients was identified. After a leave-one-out cross validation, the profile distinguished two groups of patients with different outcomes. Median overall survival and progression-free survival for the high risk group was 28.3 and 15.0 months, respectively, and was not reached by patients in the low risk group at the end of follow-up. Moreover, the profile maintained an independent prognostic value in the multivariate analysis. The hazard ratio for death was 2.3 (95% CI, 1.5 to 3.2; p<0.001).Conclusions/SignificanceIt is possible to generate a prognostic model for advanced ovarian carcinoma based on angiogenesis-related genes using formalin-fixed paraffin-embedded samples. The present results are consistent with the increasing weight of angiogenesis genes in the prognosis of ovarian carcinoma.
Highlights
Ovarian carcinoma is the most important cause of gynecological cancer-related mortality in Western societies [1]
We have focused on one of the most important events involved in carcinogenesis: angiogenesis
We have evaluated an 82 angiogenesis-related gene set in a series of 61 advanced ovarian carcinoma samples by quantitative real-time PCR
Summary
Ovarian carcinoma is the most important cause of gynecological cancer-related mortality in Western societies [1]. Outcome is significantly improved with this regimen, 60 to 70% of patients initially respond to platinum-based chemotherapy, and approximately 40 to 50% achieve complete clinical remission. Even in this last group, at least half of the patients experience a recurrence within 4 years [7]. Classical parameters such as age at diagnosis, extent of disease (as expressed as FIGO stage), residual disease after surgery, and the histopathological features of the tumor are important prognostic factors [5]. This study was planned to identify an angiogenesis-related gene expression profile with prognostic value in advanced ovarian carcinoma patients
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