Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human epithelial ovarian cancer cell lines treated with Carboplatin reveals carboplatin induced gene expression changes in vitro are prognostic of survival - time series

ABSTRACT: We performed a time-course microarray experiment to define the transcriptional response to carboplatin in vitro, and to correlate this with clinical outcome in epithelial ovarian cancer (EOC). RNA was isolated from carboplatin and control-treated 36M2 ovarian cancer cells at several time points, followed by oligonucleotide microarray hybridization. Carboplatin induced changes in gene expression were assessed at the single gene as well as at the pathway level. Clinical validation was performed in publicly available microarray datasets using disease free and overall survival endpoints. Time-course and pathway analyses identified 317 genes and 40 pathways (designated time-course and pathway signatures) deregulated following carboplatin exposure. Both types of signatures were validated in two separate platinum-treated ovarian and NSCLC cell lines using published microarray data. Expression of time-course and pathway signature genes distinguished between patients with unfavorable and favorable survival in two independent ovarian cancer datasets. Among the pathways most highly induced by carboplatin in vitro, the NRF2, NF-kB, and cytokine and inflammatory response pathways were also found to be upregulated prior to chemotherapy exposure in poor prognosis tumors. Experiment Overall Design: we treated the 36M2 cell line with carboplatin 100Î¼M or vehicle-control for 24hrs and cells were harvested and processed for RNA isolation at 24, 30 and 36hrs after treatment.

ORGANISM(S): Homo sapiens

SUBMITTER: dimitrios Spentzos

PROVIDER: E-GEOD-13525 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Carboplatin-induced gene expression changes in vitro are prognostic of survival in epithelial ovarian cancer.

Konstantinopoulos Panagiotis A PA Fountzilas Elena E Pillay Kamana K Zerbini Luiz F LF Libermann Towia A TA Cannistra Stephen A SA Spentzos Dimitrios D

BMC medical genomics 20081128

<h4>Background</h4>We performed a time-course microarray experiment to define the transcriptional response to carboplatin in vitro, and to correlate this with clinical outcome in epithelial ovarian cancer (EOC). RNA was isolated from carboplatin and control-treated 36M2 ovarian cancer cells at several time points, followed by oligonucleotide microarray hybridization. Carboplatin induced changes in gene expression were assessed at the single gene as well as at the pathway level. Clinical validati ...[more]

PMID: 19038057

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Project description:Background: Current protocols for the treatment of ovarian cancer include combination chemotherapy with a platinating agent and a taxane. However, many patients experience relapse of their cancer and the development of drug resistance is not uncommon, making successful second line therapy difficult to achieve. The objective of this study was to develop a cell line resistant to both carboplatin and docetaxel (dual drug resistant ovarian cell line A2780CBNDXL), along with single agent resistant lines (docetaxel resistant A2780DXL and carboplatin resistant A2780CBN), to investigate the mechanisms which underlie the development of dual drug resistance. Methods: The A2780 epithelial ovarian cancer cell line was used to select for isogenic carboplatin, docetaxel and dual drug resistant cell lines. A selection method of gradually increasing drug doses was implemented to avoid clonal selection. Resistance was confirmed using a clonogenic assay. Changes in gene expression associated with the development of drug resistance were determined by microarray analysis compared to parental co-culture control A2780CC. Changes in selected genes were validated by QPCR and immunoblotting. Results: Three isogenic cell lines were developed and resistance to each drug or the combination of drugs was confirmed. Development of resistance was accompanied by a reduced growth rate. The microarray and QPCR analyses showed that unique changes in gene expression occurred in the dual drug resistant cell line and that genes known to be involved in resistance could be identified in all cell lines. Conclusions: Novel changes in gene expression can occur in the development of dual drug resistance, indicating that dual drug resistance is not a simple combination of the changes occurring in single agent resistance Carboplatin, docetaxel (GSE26129) and carboplatin/docetaxel dual resistant cell lines of ovarian A2780 were generated for gene expression profilling. Two colour microarray of Agilent whole human genome nucleotide arrays was conducted with two replicate of both forward and reverse labellings for each cell line. Four arrays were used for this experiments. And it was four replicate of both forward and reverse labellings for A2780 cells. Eight arrays were used for this experiments

Dataset Information

Transcription profiling of human epithelial ovarian cancer cell lines treated with Carboplatin reveals carboplatin induced gene expression changes in vitro are prognostic of survival - time series

Publications

Carboplatin-induced gene expression changes in vitro are prognostic of survival in epithelial ovarian cancer.

Similar Datasets

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