Distinct homologous recombination gene expression profiles after neoadjuvant chemotherapy associated with clinical outcome in patients with ovarian cancer.
Gynecol Oncol
; 148(3): 553-558, 2018 03.
Article
em En
| MEDLINE
| ID: mdl-29395310
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. STUDYDESIGN:
RNA was extracted from 96 fresh frozen tumor samples from debulking surgeries from chemotherapy naïve patients with HGOC (primary derived surgeries (PDS), nâ¯=â¯55) or following neoadjuvant chemotherapy treatment (NACT), nâ¯=â¯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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Neoplasias Císticas, Mucinosas e Serosas
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Carcinoma Endometrioide
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Terapia Neoadjuvante
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Reparo de DNA por Recombinação
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Procedimentos Cirúrgicos de Citorredução
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article