Distinct homologous recombination gene expression profiles after neoadjuvant chemotherapy associated with clinical outcome in patients with ovarian cancer.

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.