Gene expression profiles predict early relapse in ovarian cancer after platinum-paclitaxel chemotherapy.

Abstract

PURPOSE:

Women with advanced epithelial ovarian cancer are routinely treated with platinum-paclitaxel chemotherapy following cytoreductive surgery, yet only approximately 20% achieve long-term disease-free survival. We hypothesized that differences in gene expression before treatment could distinguish patients with short versus long time to recurrence after administration of platinum-paclitaxel combination chemotherapy.

EXPERIMENTAL DESIGN:

To test this hypothesis, gene expression profiling of 79 primary surgically resected tumors from women with advanced-stage, high-grade epithelial ovarian cancer was done using cDNA microarrays containing 30,721 genes. Supervised learning algorithms were applied in an effort to develop a binary classifier that could discriminate women at risk for early (< or =21 months) versus late (>21 months) relapse after initial chemotherapy.

RESULTS:

A 14-gene predictive model was developed using a set of training samples (n = 51) and subsequently tested using an independent set of test samples (n = 28). This model correctly predicted the outcome of 24 of the 28 test samples (86% accuracy) with 95% positive predictive value for early relapse.

CONCLUSIONS:

Predictive markers for early recurrence can be identified for platinum-paclitaxel combination chemotherapy in primary ovarian carcinoma. The proposed 14-gene model requires further validation.

• Authors: Lynn C Hartmann, Karen H Lu, Gerald P Linette, William A Cliby, Kimberly R Kalli, David Gershenson, Robert C Bast, James Stec, Natalia Iartchouk, David I Smith, Jeffrey S Ross, Sebastian Hoersch, Viji Shridhar, James Lillie, Scott H Kaufmann, Edwin A Clark, Andrew I Damokosh
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 11 Issue 6 Pg. 2149-55 (Mar 15 2005) ISSN: 1078-0432 [Print] United States
• PMID: 15788660 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Biomarkers, Tumor
• Platinum
• Paclitaxel

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor (analysis)
• Carcinoma, Endometrioid (drug therapy, genetics, pathology)
• Cystadenocarcinoma, Serous (drug therapy, genetics, pathology)
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Middle Aged
• Neoplasm Recurrence, Local (metabolism, pathology)
• Neoplasm Staging
• Oligonucleotide Array Sequence Analysis
• Ovarian Neoplasms (drug therapy, genetics, pathology)
• Paclitaxel (administration & dosage)
• Platinum (administration & dosage)
• Survival Rate