Unique gene expression profile based on pathologic response in epithelial ovarian cancer Journal Article


Authors: Spentzos, D.; Levine, D. A.; Kolia, S.; Otu, H.; Boyd, J.; Libermann, T. A.; Cannistra, S. A.
Article Title: Unique gene expression profile based on pathologic response in epithelial ovarian cancer
Abstract: Purpose We investigated whether tumor tissue obtained at diagnosis expresses a specific gene profile that is predictive of findings at second-look surgery in patients with epithelial ovarian cancer (EOC). Patients and Methods Tumor tissue obtained at the time of diagnosis was profiled with oligonucleotide microarrays. Class prediction analysis was performed in a training set of 24 patients who had undergone a second-look procedure. The resultant predictive signature was then tested on an independent validation set comprised of 36 patients. Results A 93-gene signature referred to as the Chemotherapy Response Profile (CRP) was identified through its association with pathologic complete response. When applied to a separate validation set, the CRP distinguished between patients with unfavorable versus favorable overall survival (median 41 months v not yet reached, respectively, log-rank P = .007), with a median follow-up of 52 months. The signature maintained independent prognostic value in multivariate analysis, controlling for other known prognostic factors such as age, stage, grade, and debulking status. There was no genetic overlap between the CRP and our previously described Ovarian Cancer Prognostic Profile (OCPP), which demonstrated similar prognostic value. The combination of the CRP and OCPP yielded better prognostic discrimination then either profile alone. Genes present in the CRP include BAX a proapoptotic protein previously associated with chemotherapy response in ovarian cancer. Conclusion Identification of a gene expression profile based on pathologic response in EOC provides independent prognostic information and offers potential insights into the mechanism of drug resistance. Efforts to identify a more tailored profile using selected genes from both the CRP and OCPP are underway.
Keywords: paclitaxel; chemotherapy; classification; induced apoptosis; dna-damage; pathway; bax; b-cells; accumulation; multiple-myeloma cells
Journal Title: Journal of Clinical Oncology
Volume: 23
Issue: 31
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2005-11-01
Start Page: 7911
End Page: 7918
Language: English
DOI: 10.1200/jco.2005.02.9363
ACCESSION: WOS:000233066700024
PROVIDER: wos
PUBMED: 16204010
Notes: --- - Article - "Source: Wos"
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  1. Douglas A Levine
    380 Levine
  2. Jeffrey Boyd
    112 Boyd