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Gene Expression Profiles Associated with Response to Chemotherapy in Epithelial Ovarian Cancers

Authors' Affiliations: ¹ Laboratory of Biosystems and Cancer and ² Radiation Biology Branch, Center for Cancer Research, and ³ Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland; ⁴ Gynecology and Breast Research Laboratory, Department of Surgery, and ⁵ Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York; and ⁶ Department of Cell and Cancer Biology, Center for Cancer Research, National Cancer Institute, Rockville, Maryland

Requests for reprints: Jeff Boyd, Department of Surgery, Memorial Sloan-Kettering Cancer Center, Box 201, 1275 York Avenue, New York, NY 10021. Phone: 212-639-8608; Fax: 212-717-3538; E-mail: boydj{at}mskcc.org.

Purpose: The goal of this study was to determine whether distinct gene expression profiles are associated with intrinsic and/or acquired chemoresistance in epithelial ovarian carcinoma.

Experimental Design: Gene expression profiles were generated from 21 primary chemosensitive tumors and 24 primary chemoresistant tumors using cDNA-based microarrays. Gene expression profiles of both groups of primary tumors were then compared with those of 15 ovarian carcinomas obtained following platinum-based chemotherapy ("postchemotherapy" tumors). A theme discovery tool was used to identify functional categories of genes involved in drug resistance.

Results: Comparison of primary chemosensitive and chemoresistant tumors revealed differential expression of 85 genes (P < 0.001). Comparison of gene expression profiles of primary chemosensitive tumors and postchemotherapy tumors revealed more robust differences with 760 genes differentiating the two groups (P < 0.001). In contrast, only 230 genes were differentially expressed between primary chemoresistant and postchemotherapy groups (P < 0.001). Common to both gene lists were 178 genes representing transcripts differentially expressed between postchemotherapy tumors and all primary tumors irrespective of intrinsic chemosensitivity. The gene expression profile of postchemotherapy tumors compared with that of primary tumors revealed statistically significant overrepresentation of genes encoding extracellular matrix–related proteins.

Conclusions: These data show that gene expression profiling can discriminate primary chemoresistant from primary chemosensitive ovarian cancers. Gene expression profiles were also identified that correlate with states of intrinsic and acquired chemoresistance and that represent targets for future investigation and potential therapeutic interventions.

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