TY - JOUR
T1 - Distinct homologous recombination gene expression profiles after neoadjuvant chemotherapy associated with clinical outcome in patients with ovarian cancer
AU - Kessous, Roy
AU - Octeau, David
AU - Klein, Kathleen
AU - Tonin, Patricia N.
AU - Greenwood, Celia M.T.
AU - Pelmus, Manuela
AU - Laskov, Ido
AU - Kogan, Liron
AU - Salvador, Shannon
AU - Lau, Susie
AU - Yasmeen, Amber
AU - Gotlieb, Walter H.
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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.
KW - Gene expression
KW - High-grade ovarian cancer
KW - Homologous recombination
KW - Neoadjuvant chemotherapy
UR - http://www.scopus.com/inward/record.url?scp=85041185700&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2018.01.017
DO - 10.1016/j.ygyno.2018.01.017
M3 - Article
C2 - 29395310
AN - SCOPUS:85041185700
SN - 0090-8258
VL - 148
SP - 553
EP - 558
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 3
ER -