- •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.
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.
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.
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.
Distinct HR expression profiles define subgroups associated with overall outcome in patients that are exposed to neoadjuvant chemotherapy and not only chemotherapy-naïve patients.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Gynecologic Oncology
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- The histologic type and stage distribution of ovarian carcinomas of surface epithelial origin.Int. J. Gynecol. Pathol. 2004; 23: 41-44
- Integrated genomic analyses of ovarian carcinoma.Nature. 2011; 474: 609-615
- Prognostic factors for stage III epithelial ovarian cancer: a gynecologic oncology group study.J. Clin. Oncol. 2007; 25: 3621-3627
- Direct upregulation of STAT3 by microRNA-551b-3p deregulates growth and metastasis of ovarian cancer.Cell Rep. 2016; 15: 1493-1504
- UCA1 overexpression predicts clinical outcome of patients with ovarian cancer receiving adjuvant chemotherapy.Cancer Chemother. Pharmacol. 2016; 77: 629-634
- Current clinical application of serum biomarkers to detect ovarian cancer.Prz Menopauzalny. 2015; 14: 254-259
- Overexpression of the RNA-binding proteins Lin28B and IGF2BP3 (IMP3) is associated with chemoresistance and poor disease outcome in ovarian cancer.Br. J. Cancer. 2015; 113: 414-424
- Defects in homologous recombination repair behind the human diseases: FA and HBOC.Endocr. Relat. Cancer. 2016; 23: T19-37
- CpG island methylation of DNA damage response genes in advanced ovarian cancer.Cancer Res. 2005; 65: 8961-8967
- Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer.JAMA. 2012; 307: 382-390
- Association of BRCA1 and BRCA2 mutations with survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer.JAMA. 2011; 306: 1557-1565
- Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing.Proc. Natl. Acad. Sci. U. S. A. 2011; 108: 18032-18037
- Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene.Nat. Genet. 2010; 42: 410-414
- Hallmarks of ‘BRCAness’ in sporadic cancers.Nat. Rev. Cancer. 2004; 4: 814-819
- Somatic mutations in BRCA1 and BRCA2 could expand the number of patients that benefit from poly (ADP ribose) polymerase inhibitors in ovarian cancer.J. Clin. Oncol. 2010; 28: 3570-3576
- Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors.Nat. Med. 2003; 9: 568-574
- Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer.Cochrane Database Syst. Rev. 2015; 5CD007929
- Profiling cancer gene mutations in longitudinal epithelial ovarian cancer biopsies by targeted next-generation sequencing: a retrospective study.Ann. Oncol. 2015; 26: 1363-1371
- Analysis of Survival Data.Taylor & Francis, 1984
- Gene expression profiles predict early relapse in ovarian cancer after platinum-paclitaxel chemotherapy.Clin. Cancer Res. 2005; 11: 2149-2155
- Gene expression profile of BRCAness that correlates with responsiveness to chemotherapy and with outcome in patients with epithelial ovarian cancer.J. Clin. Oncol. 2010; 28: 3555-3561
- Gene expression profiles as prognostic markers in women with ovarian cancer.Int. J. Gynecol. Cancer. 2009; 19: 1205-1213
- Suboptimal cytoreduction in ovarian carcinoma is associated with molecular pathways characteristic of increased stromal activation.Gynecol. Oncol. 2015; 139: 394-400
- Changes in expression of genes representing key biologic processes after neoadjuvant chemotherapy in breast cancer, and prognostic implications in residual disease.Clin. Cancer Res. 2016; 22: 2405-2416
- High-throughput mutation profiling changes before and 3 weeks after chemotherapy in newly diagnosed breast cancer patients.PLoS One. 2015; 10e0142466
- Gene expression profile of residual breast cancer after doxorubicin and cyclophosphamide neoadjuvant chemotherapy.Oncol. Rep. 2009; 22: 805-813
Published online: February 03, 2018
Accepted: January 16, 2018
Received in revised form: January 14, 2018
Received: July 24, 2017
© 2018 Elsevier Inc. All rights reserved.