open access: A DNA Repair Pathway–Focused Score for Prediction of Outcomes in Ovarian Cancer Treated With Platinum-Based Chemotherapy (serous)

A DNA Repair Pathway–Focused Score for Prediction of Outcomes in Ovarian Cancer Treated With Platinum-Based Chemotherapy

Patient Samples

We extracted clinical data for 511 patients with serous ovarian cystadenocarcinoma from The Cancer Genome Atlas (TCGA) database (44) website (http://tcga-data.nci.nih.gov) on February 17, 2011, representing the largest available dataset of epithelial ovarian cancer gene expression profiles (see Supplementary Table 2, available online, for further details on which ovarian cancer samples were included in this study). These were all the patients for whom full sets of tumor gene expression data were available for download..... 


Table 1

Clinicopathologic characteristics of ovarian cancer patients in The Cancer Genome Atlas (TCGA) dataset^*

Table 2

Genes in platinum-specific DNA repair pathways that were used to construct the score^*

(For each gene, “high” means higher than median gene expression was associated with improved overall survival in The Cancer Genome Atlas dataset, and “low” means higher than median gene expression was associated with worse overall survival  

                                  ^{~~~~~~~~~~~~~~}

CONTEXT AND CAVEATS

Prior knowledge

At present, there are no effective prognostic tools for prediction of response in ovarian cancer patients, a majority of whom are diagnosed with an advanced stage (stages III and IV) and undergo surgical debulking followed by and platinum-based chemotherapy.

Study design

Gene expression data was extracted from The Cancer Genome Atlas (TCGA) database for patients with advanced ovarian cancer, and a molecular score was developed by focusing exclusively on the genes involved in platinum-induced DNA damage repair pathways. Patients were divided into low (0–10) and high (11–20) scores, and the prognostic value of the score for overall survival, recurrence-free survival, and progression-free survival was assessed. Data were validated in two independent datasets.

Contribution

Patients with high scores showed statistically significant associations with improved overall survival compared with patients with low scores. The score was predictive of overall survival, recurrence-free survival, and progression-free survival in ovarian cancer patients who received first-line platinum-based chemotherapy.

Implication

This score has the potential to become an important prognostic tool to determine whether advanced-stage ovarian cancer patients will benefit from first-line platinum-based chemotherapy.

Limitation

The score has not been tested prospectively in a clinical trial.