Originally published as JCO Early Release 10.1200/JCO.2004.04.070 on October 25 2004
Journal of Clinical Oncology, Vol 22, No 23 (December 1), 2004: pp. 4700-4710
© 2004 American Society of Clinical Oncology.
Gene Expression Signature With Independent Prognostic Significance in Epithelial Ovarian Cancer
Dimitrios Spentzos,
Douglas A. Levine,
Marco F. Ramoni,
Marie Joseph,
Xuesong Gu,
Jeff Boyd,
Towia. A. Libermann,
Stephen A. Cannistra
From the Program of Gynecologic Medical Oncology and the Genomics Center and Bioinformatics Core, Beth Israel Deaconess Medical Center; Harvard Medical School, Children’s Hospital Informatics Program and Harvard Partners Center for Genetics and Genomics, Boston, MA, and the Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
Address reprint requests to Stephen A. Cannistra, MD, Program of Gynecologic Medical Oncology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215; e-mail: scannist{at}bidmc.harvard.edu
PURPOSE: Currently available clinical and molecular prognostic factors provide an imperfect assessment of prognosis for patients with epithelial ovarian cancer (EOC). In this study, we investigated whether tumor transcription profiling could be used as a prognostic tool in this disease.
METHODS: Tumor tissue from 68 patients was profiled with oligonucleotide microarrays. Samples were randomly split into training and validation sets. A three-step training procedure was used to discover a statistically significant Kaplan-Meier split in the training set. The resultant prognostic signature was then tested on an independent validation set for confirmation.
RESULTS: In the training set, a 115-gene signature referred to as the Ovarian Cancer Prognostic Profile (OCPP) was identified. When applied to the validation set, the OCPP distinguished between patients with unfavorable and favorable overall survival (median, 30 months v not yet reached, respectively; log-rank P = .004). The signature maintained independent prognostic value in multivariate analysis, controlling for other known prognostic factors such as age, stage, grade, and debulking status. The hazard ratio for death in the unfavorable OCPP group was 4.8 (P = .021 by Cox proportional hazards analysis).
CONCLUSION: The OCPP is an independent prognostic determinant of outcome in EOC. The use of gene profiling may ultimately permit identification of EOC patients appropriate for investigational treatment approaches, based on a low likelihood of achieving prolonged survival with standard first-line platinum-based therapy.
Supported in part through grants from the Patricia Cronin Foundation, the Director’s Challenge Grant (U01 CA88175), RO1 CA85467, U24 DK58739, and through donations made to the Ovarian Cancer Research Fund at the Beth Israel Deaconess Medical Center in memory of Amy Sachs Simon.
Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, May 31-June 3, 2003, Chicago, IL.
Authors’ disclosures of potential conflicts of interest are found at the end of this article.
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