Highlights
- •Homologous recombination (HR) pathway is associated with outcome in ovarian cancer.
- •Some HR pathway genes are associated with survival before and after chemotherapy.
- •Different genes are associated with outcome before and after chemo.
Abstract
Objective
The expression of homologous recombination (HR) genes in high grade ovarian cancer
(HGOC) samples from debulking surgeries were correlated to outcomes in patients selected
for chemotherapy treatment regimens.
Study design
RNA was extracted from 96 fresh frozen tumor samples from debulking surgeries from
chemotherapy naïve patients with HGOC (primary derived surgeries (PDS), n = 55) or following neoadjuvant chemotherapy treatment (NACT), n = 41). The samples were selected for high tumor content by a gynecological pathologist,
and cancer cell content was further confirmed using a percent tumor content covariate,
and mutation score covariate analysis. Gene expression analysis was performed using
a tailored NanoString-based Pancancer Pathway Panel. Cox proportional hazard regression
models were used to assess the associations between the expression of 19 HR genes
and survival.
Results
In the PDS group, over-expression of six HR genes (C11orf30, NBN, FANCF, FANCC, FANCB,
RAD50) was associated with improved outcome, in contrast to the NACT group where four
HR genes (BRCA2, TP53, FANCB, RAD51) were associated with worse outcome. With the
adding extent of debulking as a covariate, three HR genes (NBN, FANCF, RAD50), and
only one HR gene (RAD51) remained significantly associated with survival in PDS and
NACT groups, respectively.
Conclusion
Distinct HR expression profiles define subgroups associated with overall outcome in
patients that are exposed to neoadjuvant chemotherapy and not only chemotherapy-naïve
patients.
Keywords
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Article info
Publication history
Published online: February 03, 2018
Accepted:
January 16,
2018
Received in revised form:
January 14,
2018
Received:
July 24,
2017
Identification
Copyright
© 2018 Elsevier Inc. All rights reserved.
