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

Dimitrios Spentzos, Douglas A. Levine, Shakirahmed Kolia, Hasan Otu, Jeff Boyd, Towia A. Libermann, Stephen A. Cannistra

Research output: Contribution to journalArticle

115 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)7911-7918
Number of pages8
JournalJournal of Clinical Oncology
Volume23
Issue number31
DOIs
StatePublished - Dec 1 2005

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Transcriptome
Drug Therapy
Ovarian Neoplasms
Genes
Second-Look Surgery
Combination Drug Therapy
Oligonucleotide Array Sequence Analysis
Drug Resistance
Ovarian epithelial cancer
Neoplasms
Multivariate Analysis
Survival
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Spentzos, D., Levine, D. A., Kolia, S., Otu, H., Boyd, J., Libermann, T. A., & Cannistra, S. A. (2005). Unique gene expression profile based on pathologic response in epithelial ovarian cancer. Journal of Clinical Oncology, 23(31), 7911-7918. https://doi.org/10.1200/JCO.2005.02.9363

Unique gene expression profile based on pathologic response in epithelial ovarian cancer. / Spentzos, Dimitrios; Levine, Douglas A.; Kolia, Shakirahmed; Otu, Hasan; Boyd, Jeff; Libermann, Towia A.; Cannistra, Stephen A.

In: Journal of Clinical Oncology, Vol. 23, No. 31, 01.12.2005, p. 7911-7918.

Research output: Contribution to journalArticle

Spentzos, D, Levine, DA, Kolia, S, Otu, H, Boyd, J, Libermann, TA & Cannistra, SA 2005, 'Unique gene expression profile based on pathologic response in epithelial ovarian cancer', Journal of Clinical Oncology, vol. 23, no. 31, pp. 7911-7918. https://doi.org/10.1200/JCO.2005.02.9363
Spentzos, Dimitrios ; Levine, Douglas A. ; Kolia, Shakirahmed ; Otu, Hasan ; Boyd, Jeff ; Libermann, Towia A. ; Cannistra, Stephen A. / Unique gene expression profile based on pathologic response in epithelial ovarian cancer. In: Journal of Clinical Oncology. 2005 ; Vol. 23, No. 31. pp. 7911-7918.
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