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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
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
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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.
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