Authors: | Jazaeri, A. A.; Awtrey, C. S.; Chandramouli, G. V. R.; Chuang, Y. E.; Khan, J.; Sotiriou, C.; Aprelikova, O.; Yee, C. J.; Zorn, K. K.; Birrer, M. J.; Barrett, J. C.; Boyd, J. |
Article Title: | Gene expression profiles associated with response to chemotherapy in epithelial ovarian cancers |
Abstract: | 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 chemo-sensitive 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 post-chemotherapy 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 chemo-resistant from primary chemosensitive ovarian cancers. Gene expression profiles were also identi-fied that correlate with states of intrinsic and acquired chemoresistance and that represent targets for future investigation and potential therapeutic interventions. © 2005 American Association for Cancer Research. |
Keywords: | adult; cancer chemotherapy; human tissue; aged; aged, 80 and over; middle aged; major clinical study; cisplatin; antineoplastic agents; paclitaxel; neoplasm staging; ovarian neoplasms; carboplatin; gene expression profiling; neoplasm proteins; tumor markers, biological; gene product; cyclophosphamide; drug resistance; chemosensitivity; scleroprotein; immunoenzyme techniques; gene expression regulation, neoplastic; reverse transcriptase polymerase chain reaction; oligonucleotide array sequence analysis; drug response; ovary carcinoma; platinum derivative; dna microarray; cystadenocarcinoma, serous; rna, neoplasm; carcinoma, endometrioid; postchemotherapy tumor |
Journal Title: | Clinical Cancer Research |
Volume: | 11 |
Issue: | 17 |
ISSN: | 1078-0432 |
Publisher: | American Association for Cancer Research |
Date Published: | 2005-09-01 |
Start Page: | 6300 |
End Page: | 6310 |
Language: | English |
DOI: | 10.1158/1078-0432.ccr-04-2682 |
PUBMED: | 16144934 |
PROVIDER: | scopus |
DOI/URL: | |
Notes: | --- - "Cited By (since 1996): 84" - "Export Date: 24 October 2012" - "CODEN: CCREF" - "Source: Scopus" |