A score calculated based on the expression of genes
associated with DNA repair may help to predict which patients with ovarian
cancer will respond well to platinum-based chemotherapy and have positive
“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,”
The researchers hypothesized that a molecular score
based on the expression of genes involved in platinum- induced DNA damage
repair would predict response in patients with ovarian cancer.
To test this theory, they gathered data from The Cancer
Genome Atlas for 151 DNA repair genes from tumors of 511 patients with serous
ovarian cystadenocarcinoma. From these 151 genes, they narrowed the scope to 23
genes from four pathways (ATM, FA/HR, NER and TLS).
Based on the presence of these genes, patients were
assigned a score: low for patients with scores of 0 to 10 and high for those
with scores from 11 to 20.
Results indicated that low scores were associated with
worse survival outcomes. Five-year survival in patients with low scores was 17%
vs. 40% in patients with high scores. The median OS was 3 years for low scores
vs. 4.5 years for high scores. The gene score was the only factor that was
linked with OS (high vs. low scores HR=0.40; 95% CI, 0.32-0.66).
The score also was able to predict the likelihood that a
patient would achieve a complete response. When patients were classified into
the lowest, intermediate or highest tertiles for scores, these were associated
with the lowest, intermediate and highest likelihood for complete response.
Increasing likelihood for complete response was associated with increased
likelihood for survival (see chart).
The researchers then validated these results in two gene
expression microarray datasets.
“With additional prospective validation in clinical
trials, we hope that the score can become a powerful tool that is useful in
stratifying advanced-stage ovarian cancer patients toward optimal treatments
incorporating new treatment regimens vs. current standard of care,” the
- Kang J. J Natl Cancer Inst. 2012;104:670-681.